Prognostic Implications of Immunohistochemical Biomarkers in Non-muscle-invasive Blad Cancer and Muscle-invasive Bladder Cancer

Author(s): Martin Boegemann, Laura-Maria Krabbe*

Journal Name: Mini-Reviews in Medicinal Chemistry

Volume 20 , Issue 12 , 2020

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Urothelial carcinoma of the bladder (UCB) is a very heterogeneous disease and divided into invasive and non-invasive disease. In non-muscle-invasive bladder cancer (NMIBC), recurrence after transurethral resection or instillation-therapy, and progression to invasive disease are issues of concern. In muscle-invasive bladder cancer (MIBC), systemic recurrence after radical treatment is a pressing problem, as the available therapies in this setting are of limited efficacy. For both entities there are only few clinicopathological prognostic biomarkers to identify subgroups at risk to aid in decision making to whom to offer early radical cystectomy in case of NMIBC or neoadjuvant/adjuvant chemotherapy in case of MIBC to improve outcomes. Despite advances in surgery and intravesical therapy, up to 30% of NMIBC-patients suffer progression to MIBC. After cystectomy around 50% of MIBC patients suffer local or systemic recurrence and subsequently succumb to the disease. Standard features, like pathological staging and grading, are not sufficient to identify patients at risk beyond doubt. Recent advances in molecular diagnostics in combination with standard pathological features could be used to improve risk stratification of patients, guide treatment plans and ultimately improve outcomes. Immunohistochemical (IHC) analysis can detect altered regulatory pathway-products. Until now a plethora of prognostic IHC-biomarkers has been reported on in UCB, but only few have been validated and no biomarker is in routine use or recommended by guidelines. In this review we discuss the prognostic potential of the most promising IHC-biomarkers in NMIBC and MIBC with a focus on prognostication of recurrence and stage progression in NMIBC as well as recurrence-free, cancer-specific and overall survival in MIBC.

Keywords: Biomarkers, bladder cancer, immunohistochemistry, muscle-invasive, non-muscle-invasive, prognostic.

Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2016. CA Cancer J. Clin., 2016, 66(1), 7-30.
[] [PMID: 26742998]
Kirkali, Z.; Chan, T.; Manoharan, M.; Algaba, F.; Busch, C.; Cheng, L.; Kiemeney, L.; Kriegmair, M.; Montironi, R.; Murphy, W.M.; Sesterhenn, I.A.; Tachibana, M.; Weider, J. Bladder cancer: epidemiology, staging and grading, and diagnosis. Urology, 2005, 66(6)(Suppl. 1), 4-34.
[] [PMID: 16399414]
Hautmann, R.E.; Gschwend, J.E.; de Petriconi, R.C.; Kron, M.; Volkmer, B.G. Cystectomy for transitional cell carcinoma of the bladder: results of a surgery only series in the neobladder era. J. Urol., 2006, 176(2), 486-492.
[] [PMID: 16813874]
Shariat, S.F.; Karakiewicz, P.I.; Palapattu, G.S.; Lotan, Y.; Rogers, C.G.; Amiel, G.E.; Vazina, A.; Gupta, A.; Bastian, P.J.; Sagalowsky, A.I.; Schoenberg, M.P.; Lerner, S.P. Outcomes of radical cystectomy for transitional cell carcinoma of the bladder: a contemporary series from the Bladder Cancer Research Consortium. J. Urol., 2006, 176(6 Pt 1), 2414-2422.
[] [PMID: 17085118]
Stein, J.P.; Lieskovsky, G.; Cote, R.; Groshen, S.; Feng, A.C.; Boyd, S.; Skinner, E.; Bochner, B.; Thangathurai, D.; Mikhail, M.; Raghavan, D.; Skinner, D.G. Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. J. Clin. Oncol., 2001, 19(3), 666-675.
[] [PMID: 11157016]
Malgor, R.; Crouser, S.; Greco, D.; Brockett, C.; Coschigano, K.; Nakazawa, M.; Jenkinson, S. Correlation of Wnt5a expression with histopathological grade/stage in urothelial carcinoma of the bladder. Diagn. Pathol., 2013, 8, 139.
[] [PMID: 23947922]
Kim, W.J.; Kim, Y.J. Epigenetics of bladder cancer. Methods Mol. Biol., 2012, 863, 111-118.
[] [PMID: 22359289]
Shariat, S.F.; Karakiewicz, P.I.; Ashfaq, R.; Lerner, S.P.; Palapattu, G.S.; Cote, R.J.; Sagalowsky, A.I.; Lotan, Y. Multiple biomarkers improve prediction of bladder cancer recurrence and mortality in patients undergoing cystectomy. Cancer, 2008, 112(2), 315-325.
[] [PMID: 18008359]
Shariat, S.F.; Tilki, D. Bladder cancer: nomogram aids clinical decision making after radical cystectomy. Nat. Rev. Urol., 2010, 7(4), 182-184.
[] [PMID: 20383183]
Vrooman, O.P.; Witjes, J.A. Molecular markers for detection, surveillance and prognostication of bladder cancer. Int. J. Urol., 2009, 16(3), 234-243.
[] [PMID: 19298346]
Addeo, R.; Caraglia, M.; Bellini, S.; Abbruzzese, A.; Vincenzi, B.; Montella, L.; Miragliuolo, A.; Guarrasi, R.; Lanna, M.; Cennamo, G.; Faiola, V.; Del Prete, S. Randomized phase III trial on gemcitabine versus mytomicin in recurrent superficial bladder cancer: evaluation of efficacy and tolerance. J. Clin. Oncol., 2010, 28(4), 543-548.
[] [PMID: 19841330]
Williams, SG; Buscarini, M; Stein, JP Molecular markers for diagnosis, staging, and prognosis of bladder cancer., 2001, 15, 1461-70.
Cordon-Cardo, C. Mutations of cell cycle regulators. Biological and clinical implications for human neoplasia. Am. J. Pathol., 1995, 147(3), 545-560.
[PMID: 7677168]
Bassily, N.H.; Vallorosi, C.J.; Akdas, G.; Montie, J.E.; Rubin, M.A. Coordinate expression of cytokeratins 7 and 20 in prostate adenocarcinoma and bladder urothelial carcinoma. Am. J. Clin. Pathol., 2000, 113(3), 383-388.
[] [PMID: 10705819]
Buza, N.; Cohen, P.J.; Pei Hui, ; Parkash, V. Inverse p16 and p63 expression in small cell carcinoma and high-grade urothelial cell carcinoma of the urinary bladder. Int. J. Surg. Pathol., 2010, 18(2), 94-102.
[] [PMID: 20164052]
Grotemeyer, K.H. The platelet-reactivity-test--a useful “by-product” of the blood-sampling procedure? Thromb. Res., 1991, 61(4), 423-431.
[] [PMID: 1905849]
Lane, D.P. Cancer. p53, guardian of the genome. Nature, 1992, 358(6381), 15-16.
[] [PMID: 1614522]
Shariat, S.F.; Ashfaq, R.; Sagalowsky, A.I.; Lotan, Y. Predictive value of cell cycle biomarkers in nonmuscle invasive bladder transitional cell carcinoma. J. Urol., 2007, 177(2), 481-487.
[] [PMID: 17222615]
Shariat, S.F.; Zlotta, A.R.; Ashfaq, R.; Sagalowsky, A.I.; Lotan, Y. Cooperative effect of cell-cycle regulators expression on bladder cancer development and biologic aggressiveness. Mod. Pathol., 2007, 20(4), 445-459.
[] [PMID: 17384651]
Shariat, S.F.; Lotan, Y.; Karakiewicz, P.I.; Ashfaq, R.; Isbarn, H.; Fradet, Y.; Bastian, P.J.; Nielsen, M.E.; Capitanio, U.; Jeldres, C.; Montorsi, F.; Müller, S.C.; Karam, J.A.; Heukamp, L.C.; Netto, G.; Lerner, S.P.; Sagalowsky, A.I.; Cote, R.J. p53 predictive value for pT1-2 N0 disease at radical cystectomy. J. Urol., 2009, 182(3), 907-913.
[] [PMID: 19616250]
Malats, N.; Bustos, A.; Nascimento, C.M.; Fernandez, F.; Rivas, M.; Puente, D.; Kogevinas, M.; Real, F.X. P53 as a prognostic marker for bladder cancer: a meta-analysis and review. Lancet Oncol., 2005, 6(9), 678-686.
[] [PMID: 16129368]
Wang, L.; Feng, C.; Ding, G.; Ding, Q.; Zhou, Z.; Jiang, H.; Wu, Z. Ki67 and TP53 expressions predict recurrence of non-muscle-invasive bladder cancer. Tumour Biol., 2014, 35(4), 2989-2995.
[] [PMID: 24241960]
Grossman, H.B.; Liebert, M.; Antelo, M.; Dinney, C.P.; Hu, S.X.; Palmer, J.L.; Benedict, W.F. p53 and RB expression predict progression in T1 bladder cancer. Clin. Cancer Res., 1998, 4(4), 829-834.
[PMID: 9563875]
Shariat, S.F.; Weizer, A.Z.; Green, A.; Laucirica, R.; Frolov, A.; Wheeler, T.M.; Lerner, S.P. Prognostic value of P53 nuclear accumulation and histopathologic features in T1 transitional cell carcinoma of the urinary bladder. Urology, 2000, 56(5), 735-740.
[] [PMID: 11068290]
Shariat, S.F.; Bolenz, C.; Godoy, G.; Fradet, Y.; Ashfaq, R.; Karakiewicz, P.I.; Isbarn, H.; Jeldres, C.; Rigaud, J.; Sagalowsky, A.I.; Lotan, Y. Predictive value of combined immunohistochemical markers in patients with pT1 urothelial carcinoma at radical cystectomy. J. Urol., 2009, 182(1), 78-84. [discussion].
[] [PMID: 19447418]
Goebell, P.J.; Groshen, S.G.; Schmitz-Dräger, B.J. p53 immunohistochemistry in bladder cancer--a new approach to an old question. Urol. Oncol., 2010, 28(4), 377-388.
[] [PMID: 20610276]
López-Knowles, E.; Hernández, S.; Kogevinas, M.; Lloreta, J.; Amorós, A.; Tardón, A.; Carrato, A.; Kishore, S.; Serra, C.; Malats, N.; Real, F.X. The p53 pathway and outcome among patients with T1G3 bladder tumors. Clin. Cancer Res., 2006, 12(20 Pt 1), 6029-6036.
[] [PMID: 17062677]
Esuvaranathan, K.; Chiong, E.; Thamboo, T.P.; Chan, Y.H.; Kamaraj, R.; Mahendran, R.; Teh, M. Predictive value of p53 and pRb expression in superficial bladder cancer patients treated with BCG and interferon-alpha. Cancer, 2007, 109(6), 1097-1105.
[] [PMID: 17311305]
Oh, J.J.; Ji, S.H.; Choi, D.K.; Gong, I.H.; Kim, T.H.; Park, D.S. A six-week course of bacillus Calmette-Guérin prophylaxis is insufficient to prevent tumor recurrence in nonmuscle invasive bladder cancer with strong-positive expression of p53. Oncology, 2010, 79(5-6), 440-446.
[] [PMID: 21487231]
Park, J.; Song, C.; Shin, E.; Hong, J.H.; Kim, C.S.; Ahn, H. Do molecular biomarkers have prognostic value in primary T1G3 bladder cancer treated with bacillus Calmette-Guerin intravesical therapy? Urol. Oncol., 2013, 31(6), 849-856.
[] [PMID: 21782482]
van Rhijn, B.W.; Liu, L.; Vis, A.N.; Bostrom, P.J.; Zuiverloon, T.C.; Fleshner, N.E.; van der Aa, M.N.; Alkhateeb, S.S.; Bangma, C.H.; Jewett, M.A.; Zwarthoff, E.C.; Bapat, B.; van der Kwast, T.H.; Zlotta, A.R. Prognostic value of molecular markers, sub-stage and European Organisation for the Research and Treatment of Cancer risk scores in primary T1 bladder cancer. BJU Int., 2012, 110(8), 1169-1176.
[] [PMID: 22448597]
Zhou, X.; Zhang, G.; Tian, Y. p53 Status correlates with the risk of recurrence in non-muscle invasive bladder cancers treated with Bacillus Calmette-Guérin: a meta-analysis. PLoS One, 2015, 10(3)e0119476
[] [PMID: 25742650]
Dalbagni, G.; Presti, J.; Reuter, V.; Fair, W.R.; Cordon-Cardo, C. Genetic alterations in bladder cancer. Lancet, 1993, 342(8869), 469-471.
[] [PMID: 8102431]
Knowles, M.A.; Elder, P.A.; Williamson, M.; Cairns, J.P.; Shaw, M.E.; Law, M.G. Allelotype of human bladder cancer. Cancer Res., 1994, 54(2), 531-538.
[PMID: 8275491]
Chatterjee, S.J.; Datar, R.; Youssefzadeh, D.; George, B.; Goebell, P.J.; Stein, J.P.; Young, L.; Shi, S.R.; Gee, C.; Groshen, S.; Skinner, D.G.; Cote, R.J. Combined effects of p53, p21, and pRb expression in the progression of bladder transitional cell carcinoma. J. Clin. Oncol., 2004, 22(6), 1007-1013.
[] [PMID: 14981105]
Shariat, S.F.; Tokunaga, H.; Zhou, J.; Kim, J.; Ayala, G.E.; Benedict, W.F.; Lerner, S.P. p53, p21, pRB, and p16 expression predict clinical outcome in cystectomy with bladder cancer. J. Clin. Oncol., 2004, 22(6), 1014-1024.
[] [PMID: 14981102]
Shariat, S.F.; Chade, D.C.; Karakiewicz, P.I.; Ashfaq, R.; Isbarn, H.; Fradet, Y.; Bastian, P.J.; Nielsen, M.E.; Capitanio, U.; Jeldres, C.; Montorsi, F.; Lerner, S.P.; Sagalowsky, A.I.; Cote, R.J.; Lotan, Y. Combination of multiple molecular markers can improve prognostication in patients with locally advanced and lymph node positive bladder cancer. J. Urol., 2010, 183(1), 68-75.
[] [PMID: 19913255]
Shariat, S.F.; Kim, J.; Raptidis, G.; Ayala, G.E.; Lerner, S.P. Association of p53 and p21 expression with clinical outcome in patients with carcinoma in situ of the urinary bladder. Urology, 2003, 61(6), 1140-1145.
[] [PMID: 12809883]
Shariat, S.F.; Bolenz, C.; Karakiewicz, P.I.; Fradet, Y.; Ashfaq, R.; Bastian, P.J.; Nielsen, M.E.; Capitanio, U.; Jeldres, C.; Rigaud, J.; Müller, S.C.; Lerner, S.P.; Montorsi, F.; Sagalowsky, A.I.; Cote, R.J.; Lotan, Y. p53 expression in patients with advanced urothelial cancer of the urinary bladder. BJU Int., 2010, 105(4), 489-495.
[] [PMID: 19659466]
Shariat, S.F.; Chromecki, T.F.; Cha, E.K.; Karakiewicz, P.I.; Sun, M.; Fradet, Y.; Isbarn, H.; Scherr, D.S.; Bastian, P.J.; Pummer, K.; Fajkovic, H.; Sagalowsky, A.I.; Ashfaq, R.; Doblinger, M.; Cote, R.J.; Lotan, Y. Risk stratification of organ confined bladder cancer after radical cystectomy using cell cycle related biomarkers. J. Urol., 2012, 187(2), 457-462.
[] [PMID: 22177145]
Stadler, W.M.; Lerner, S.P.; Groshen, S.; Stein, J.P.; Shi, S.R.; Raghavan, D.; Esrig, D.; Steinberg, G.; Wood, D.; Klotz, L.; Hall, C.; Skinner, D.G.; Cote, R.J. Phase III study of molecularly targeted adjuvant therapy in locally advanced urothelial cancer of the bladder based on p53 status. J. Clin. Oncol., 2011, 29(25), 3443-3449.
[] [PMID: 21810677]
Shariat, S.F.; Lotan, Y.; Vickers, A.; Karakiewicz, P.I.; Schmitz-Dräger, B.J.; Goebell, P.J.; Malats, N. Statistical consideration for clinical biomarker research in bladder cancer. Urol. Oncol., 2010, 28(4), 389-400.
[] [PMID: 20610277]
Tokunaga, H.; Shariat, S.F.; Green, A.E.; Brown, R.M.; Zhou, J.H.; Benedict, W.F.; Lerner, S.P. Correlation of immunohistochemical molecular staging of bladder biopsies and radical cystectomy specimens. Int. J. Radiat. Oncol. Biol. Phys., 2001, 51(1), 16-22.
[] [PMID: 11516846]
Blandino, G.; Levine, A.J.; Oren, M. Mutant p53 gain of function: differential effects of different p53 mutants on resistance of cultured cells to chemotherapy. Oncogene, 1999, 18(2), 477-485.
[] [PMID: 9927204]
Strano, S.; Dell’Orso, S.; Di Agostino, S.; Fontemaggi, G.; Sacchi, A.; Blandino, G. Mutant p53: an oncogenic transcription factor. Oncogene, 2007, 26(15), 2212-2219.
[] [PMID: 17401430]
Weisz, L.; Oren, M.; Rotter, V. Transcription regulation by mutant p53. Oncogene, 2007, 26(15), 2202-2211.
[] [PMID: 17401429]
Soussi, T. p53 alterations in human cancer: more questions than answers. Oncogene, 2007, 26(15), 2145-2156.
[] [PMID: 17401423]
Schmitz-Dräger, B.J.; Goebell, P.J.; Ebert, T.; Fradet, Y. p53 immunohistochemistry as a prognostic marker in bladder cancer. Playground for urology scientists? Eur. Urol., 2000, 38(6), 691-699.
[] [PMID: 11111186]
McShane, L.M.; Aamodt, R.; Cordon-Cardo, C.; Cote, R.; Faraggi, D.; Fradet, Y.; Grossman, H.B.; Peng, A.; Taube, S.E.; Waldman, F.M. Reproducibility of p53 immunohistochemistry in bladder tumors. National Cancer Institute, Bladder Tumor Marker Network. Clin. Cancer Res., 2000, 6(5), 1854-1864.
[PMID: 10815908]
Sanchez-Carbayo, M.; Socci, N.D.; Kirchoff, T.; Erill, N.; Offit, K.; Bochner, B.H.; Cordon-Cardo, C. A polymorphism in HDM2 (SNP309) associates with early onset in superficial tumors, TP53 mutations, and poor outcome in invasive bladder cancer. Clin. Cancer Res., 2007, 13(11), 3215-3220.
[] [PMID: 17545525]
Stein, J.P.; Ginsberg, D.A.; Grossfeld, G.D.; Chatterjee, S.J.; Esrig, D.; Dickinson, M.G.; Groshen, S.; Taylor, C.R.; Jones, P.A.; Skinner, D.G.; Cote, R.J. Effect of p21WAF1/CIP1 expression on tumor progression in bladder cancer. J. Natl. Cancer Inst., 1998, 90(14), 1072-1079.
[] [PMID: 9672255]
Tang, K.; Wang, C.; Chen, Z.; Xu, H.; Ye, Z. Clinicopathologic and prognostic significance of p21 (Cip1/Waf1) expression in bladder cancer. Int. J. Clin. Exp. Pathol., 2015, 8(5), 4999-5007.
[PMID: 26191193]
Migaldi, M.; Sgambato, A.; Garagnani, L.; Ardito, R.; Ferrari, P.; De Gaetani, C.; Cittadini, A.; Trentini, G.P. Loss of p21Waf1 expression is a strong predictor of reduced survival in primary superficial bladder cancers. Clin. Cancer Res., 2000, 6(8), 3131-3138.
[PMID: 10955794]
Behnsawy, H.M.; Miyake, H.; Abdalla, M.A.; Sayed, M.A.; Ahmed, Ael-F.; Fujisawa, M. Expression of cell cycle-associated proteins in non-muscle-invasive bladder cancer: correlation with intravesical recurrence following transurethral resection. Urol. Oncol., 2011, 29(5), 495-501.
[] [PMID: 19914103]
Liukkonen, T.; Lipponen, P.; Raitanen, M.; Kaasinen, E.; Ala-Opas, M.; Rajala, P.; Kosma, V.M. Evaluation of p21WAF1/CIP1 and cyclin D1 expression in the progression of superficial bladder cancer. Urol. Res., 2000, 28(5), 285-292.
[] [PMID: 11127704]
Kuczyk, M.A.; Machtens, S.; Bokemeyer, C.; Hradil, K.; Macheel, I.; Jetscho, V.; Hartmann, J.; Thon, W.F.; Jonas, U.; Serth, J. Prognostic value of p27Kip1 and p21WAF/Cip protein expression in muscle invasive bladder cancer. Oncol. Rep., 1999, 6(3), 687-693.
[] [PMID: 10203616]
Korkolopoulou, P.; Konstantinidou, A.E.; Thomas-Tsagli, E.; Christodoulou, P.; Kapralos, P.; Davaris, P. WAF1/p21 protein expression is an independent prognostic indicator in superficial and invasive bladder cancer. Appl. Immunohistochem. Mol. Morphol., 2000, 8(4), 285-292.
[] [PMID: 11127920]
Koga, F.; Kitahara, S.; Arai, K.; Honda, M.; Sumi, S.; Yoshida, K. Negative p53/positive p21 immunostaining is a predictor of favorable response to chemotherapy in patients with locally advanced bladder cancer. Jpn. J. Cancer Res., 2000, 91(4), 416-423.
[] [PMID: 10804290]
Qureshi, K.N.; Griffiths, T.R.; Robinson, M.C.; Marsh, C.; Roberts, J.T.; Lunec, J.; Neal, D.E.; Mellon, J.K. Combined p21WAF1/CIP1 and p53 overexpression predict improved survival in muscle-invasive bladder cancer treated by radical radiotherapy. Int. J. Radiat. Oncol. Biol. Phys., 2001, 51(5), 1234-1240.
[] [PMID: 11728682]
Sherr, C.J.; Roberts, J.M. CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev., 1999, 13(12), 1501-1512.
[] [PMID: 10385618]
Korkolopoulou, P.; Christodoulou, P.; Konstantinidou, A.E.; Thomas-Tsagli, E.; Kapralos, P.; Davaris, P. Cell cycle regulators in bladder cancer: a multivariate survival study with emphasis on p27Kip1. Hum. Pathol., 2000, 31(6), 751-760.
[] [PMID: 10872671]
Sgambato, A.; Migaldi, M.; Faraglia, B.; Garagnani, L.; Romano, G.; De Gaetani, C.; Ferrari, P.; Capelli, G.; Trentini, G.P.; Cittadini, A. Loss of P27Kip1 expression correlates with tumor grade and with reduced disease-free survival in primary superficial bladder cancers. Cancer Res., 1999, 59(13), 3245-3250.
[PMID: 10397272]
Schrier, B.P.; Vriesema, J.L.; Witjes, J.A.; Kiemeney, L.A.; Schalken, J.A. The predictive value of p53, p27(kip1), and alpha-catenin for progression in superficial bladder carcinoma. Eur. Urol., 2006, 50(1), 76-82.
[] [PMID: 16413663]
Lopez-Beltran, A.; Luque, R.J.; Alvarez-Kindelan, J.; Quintero, A.; Merlo, F.; Carrasco, J.C.; Requena, M.J.; Montironi, R. Prognostic factors in stage T1 grade 3 bladder cancer survival: the role of G1-S modulators (p53, p21Waf1, p27kip1, Cyclin D1, and Cyclin D3) and proliferation index (ki67-MIB1). Eur. Urol., 2004, 45(5), 606-612.
[] [PMID: 15082203]
Rabbani, F.; Koppie, T.M.; Charytonowicz, E.; Drobnjak, M.; Bochner, B.H.; Cordon-Cardo, C. Prognostic significance of p27Kip1 expression in bladder cancer. BJU Int., 2007, 100(2), 259-263.
[] [PMID: 17555476]
Bartoletti, R.; Cai, T.; Nesi, G.; Roberta Girardi, L.; Baroni, G.; Dal Canto, M. Loss of P16 expression and chromosome 9p21 LOH in predicting outcome of patients affected by superficial bladder cancer. J. Surg. Res., 2007, 143(2), 422-427.
[] [PMID: 17612565]
Olsson, H.; Hultman, P.; Monsef, N.; Rosell, J.; Jahnson, S. Immunohistochemical evaluation of cell cycle regulators: impact on predicting prognosis in stage t1 urinary bladder cancer. ISRN Urol., 2012, 2012379081
[] [PMID: 23304558]
Fung, Y.K.; Murphree, A.L.; T’Ang, A.; Qian, J.; Hinrichs, S.H.; Benedict, W.F. Structural evidence for the authenticity of the human retinoblastoma gene. Science, 1987, 236(4809), 1657-1661.
[] [PMID: 2885916]
Yurakh, A.O.; Ramos, D.; Calabuig-Fariñas, S.; López-Guerrero, J.A.; Rubio, J.; Solsona, E.; Romanenko, A.M.; Vozianov, A.F.; Pellin, A.; Llombart-Bosch, A. Molecular and immunohistochemical analysis of the prognostic value of cell-cycle regulators in urothelial neoplasms of the bladder. Eur. Urol., 2006, 50(3), 506-515.
[] [PMID: 16624482]
Scholzen, T.; Gerdes, J. The Ki-67 protein: from the known and the unknown. J. Cell. Physiol., 2000, 182(3), 311-322.
[<311:AID-JCP1>3.0.CO;2-9] [PMID: 10653597]
Quintero, A.; Alvarez-Kindelan, J.; Luque, R.J.; Gonzalez-Campora, R.; Requena, M.J.; Montironi, R.; Lopez-Beltran, A. Ki-67 MIB1 labelling index and the prognosis of primary TaT1 urothelial cell carcinoma of the bladder. J. Clin. Pathol., 2006, 59(1), 83-88.
[] [PMID: 16394286]
Bertz, S.; Otto, W.; Denzinger, S.; Wieland, W.F.; Burger, M.; Stöhr, R.; Link, S.; Hofstädter, F.; Hartmann, A. Combination of CK20 and Ki-67 immunostaining analysis predicts recurrence, progression, and cancer-specific survival in pT1 urothelial bladder cancer. Eur. Urol., 2014, 65(1), 218-226.
[] [PMID: 22633802]
Seo, H.K.; Cho, K.S.; Chung, J.; Joung, J.Y.; Park, W.S.; Chung, M.K. Prognostic value of p53 and Ki-67 expression in intermediate-risk patients with nonmuscle-invasive bladder cancer receiving adjuvant intravesical mitomycin C therapy. Urology, 2010, 76(512), 1-7.
Margulis, V.; Shariat, S.F.; Ashfaq, R.; Sagalowsky, A.I.; Lotan, Y. Ki-67 is an independent predictor of bladder cancer outcome in patients treated with radical cystectomy for organ-confined disease. Clin. Cancer Res., 2006, 12(24), 7369-7373.
[] [PMID: 17189409]
Margulis, V.; Lotan, Y.; Karakiewicz, P.I.; Fradet, Y.; Ashfaq, R.; Capitanio, U.; Montorsi, F.; Bastian, P.J.; Nielsen, M.E.; Müller, S.C.; Rigaud, J.; Heukamp, L.C.; Netto, G.; Lerner, S.P.; Sagalowsky, A.I.; Shariat, S.F. Multi-institutional validation of the predictive value of Ki-67 labeling index in patients with urinary bladder cancer. J. Natl. Cancer Inst., 2009, 101(2), 114-119.
[] [PMID: 19141773]
Lotan, Y.; Bagrodia, A.; Passoni, N.; Rachakonda, V.; Kapur, P.; Arriaga, Y.; Bolenz, C.; Margulis, V.; Raj, G.V.; Sagalowsky, A.I.; Shariat, S.F. Prospective evaluation of a molecular marker panel for prediction of recurrence and cancer-specific survival after radical cystectomy. Eur. Urol., 2013, 64(3), 465-471.
[] [PMID: 23571005]
Richter, J.; Wagner, U.; Kononen, J.; Fijan, A.; Bruderer, J.; Schmid, U.; Ackermann, D.; Maurer, R.; Alund, G.; Knönagel, H.; Rist, M.; Wilber, K.; Anabitarte, M.; Hering, F.; Hardmeier, T.; Schönenberger, A.; Flury, R.; Jäger, P.; Fehr, J.L.; Schraml, P.; Moch, H.; Mihatsch, M.J.; Gasser, T.; Kallioniemi, O.P.; Sauter, G. High-throughput tissue microarray analysis of cyclin E gene amplification and overexpression in urinary bladder cancer. Am. J. Pathol., 2000, 157(3), 787-794.
[] [PMID: 10980118]
Del Pizzo, J.J.; Borkowski, A.; Jacobs, S.C.; Kyprianou, N. Loss of cell cycle regulators p27(Kip1) and cyclin E in transitional cell carcinoma of the bladder correlates with tumor grade and patient survival. Am. J. Pathol., 1999, 155(4), 1129-1136.
[] [PMID: 10514396]
Shariat, S.F.; Ashfaq, R.; Sagalowsky, A.I.; Lotan, Y. Correlation of cyclin D1 and E1 expression with bladder cancer presence, invasion, progression, and metastasis. Hum. Pathol., 2006, 37(12), 1568-1576.
[] [PMID: 16949911]
Kim, J.K.; Diehl, J.A. Nuclear cyclin D1: an oncogenic driver in human cancer. J. Cell. Physiol., 2009, 220(2), 292-296.
[] [PMID: 19415697]
Shariat, S.F.; Ashfaq, R.; Sagalowsky, A.I.; Lotan, Y. Association of cyclin D1 and E1 expression with disease progression and biomarkers in patients with nonmuscle-invasive urothelial cell carcinoma of the bladder. Urol. Oncol., 2007, 25(6), 468-475.
[] [PMID: 18047954]
Seiler, R.; Thalmann, G.N.; Rotzer, D.; Perren, A.; Fleischmann, A. CCND1/CyclinD1 status in metastasizing bladder cancer: a prognosticator and predictor of chemotherapeutic response. Mod. Pathol., 2014, 27(1), 87-95.
[] [PMID: 23887292]
Ren, B.; Li, W.; Yang, Y.; Wu, S. The impact of cyclin D1 overexpression on the prognosis of bladder cancer: a meta-analysis. World J. Surg. Oncol., 2014, 12, 55.
[] [PMID: 24602161]
McKnight, J.J.; Gray, S.B.; O’Kane, H.F.; Johnston, S.R.; Williamson, K.E. Apoptosis and chemotherapy for bladder cancer. J. Urol., 2005, 173(3), 683-690.
[] [PMID: 15711244]
Wajant, H. The Fas signaling pathway: more than a paradigm. Science, 2002, 296(5573), 1635-1636.
[] [PMID: 12040174]
Yamana, K.; Bilim, V.; Hara, N.; Kasahara, T.; Itoi, T.; Maruyama, R.; Nishiyama, T.; Takahashi, K.; Tomita, Y. Prognostic impact of FAS/CD95/APO-1 in urothelial cancers: decreased expression of Fas is associated with disease progression. Br. J. Cancer, 2005, 93(5), 544-551.
[] [PMID: 16091761]
Maas, S.; Warskulat, U.; Steinhoff, C.; Mueller, W.; Grimm, M.O.; Schulz, W.A.; Seifert, H.H. Decreased Fas expression in advanced-stage bladder cancer is not related to p53 status. Urology, 2004, 63(2), 392-397.
[] [PMID: 14972509]
Arai, M.; Sasaki, A.; Saito, N.; Nakazato, Y. Immunohistochemical analysis of cleaved caspase-3 detects high level of apoptosis frequently in diffuse large B-cell lymphomas of the central nervous system. Pathol. Int., 2005, 55(3), 122-129.
[] [PMID: 15743320]
Burton, P.B.; Anderson, C.J.; Corbishly, C.M. Caspase 3 and p27 as predictors of invasive bladder cancer. N. Engl. J. Med., 2000, 343(19), 1418-1420.
[] [PMID: 11183887]
Wang, J.; Zhang, X.; Wei, P.; Zhang, J.; Niu, Y.; Kang, N.; Zhang, Y.; Zhang, W.; Xing, N. Livin, Survivin and Caspase 3 as early recurrence markers in non-muscle-invasive bladder cancer. World J. Urol., 2014, 32(6), 1477-1484.
[] [PMID: 24595485]
Karam, J.A.; Lotan, Y.; Karakiewicz, P.I.; Ashfaq, R.; Sagalowsky, A.I.; Roehrborn, C.G.; Shariat, S.F. Use of combined apoptosis biomarkers for prediction of bladder cancer recurrence and mortality after radical cystectomy. Lancet Oncol., 2007, 8(2), 128-136.
[] [PMID: 17267327]
Kong, G.; Shin, K.Y.; Oh, Y.H.; Lee, J.J.; Park, H.Y.; Woo, Y.N.; Lee, J.D. Bcl-2 and p53 expressions in invasive bladder cancers. Acta Oncol., 1998, 37(7-8), 715-720.
[] [PMID: 10050992]
Ong, F.; Moonen, L.M.; Gallee, M.P.; ten Bosch, C.; Zerp, S.F.; Hart, A.A.; Bartelink, H.; Verheij, M. Prognostic factors in transitional cell cancer of the bladder: an emerging role for Bcl-2 and p53. Radiother. Oncol., 2001, 61(2), 169-175.
[] [PMID: 11690683]
Ambrosini, G.; Adida, C.; Altieri, D.C. A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat. Med., 1997, 3(8), 917-921.
[] [PMID: 9256286]
Altieri, D.C. Survivin, versatile modulation of cell division and apoptosis in cancer. Oncogene, 2003, 22(53), 8581-8589.
[] [PMID: 14634620]
Salz, W.; Eisenberg, D.; Plescia, J.; Garlick, D.S.; Weiss, R.M.; Wu, X.R.; Sun, T.T.; Altieri, D.C. A survivin gene signature predicts aggressive tumor behavior. Cancer Res., 2005, 65(9), 3531-3534.
[] [PMID: 15867343]
Karam, J.A.; Lotan, Y.; Ashfaq, R.; Sagalowsky, A.I.; Shariat, S.F. Survivin expression in patients with non-muscle-invasive urothelial cell carcinoma of the bladder. Urology, 2007, 70(3), 482-486.
[] [PMID: 17905101]
Shariat, S.F.; Ashfaq, R.; Karakiewicz, P.I.; Saeedi, O.; Sagalowsky, A.I.; Lotan, Y. Survivin expression is associated with bladder cancer presence, stage, progression, and mortality. Cancer, 2007, 109(6), 1106-1113.
[] [PMID: 17311310]
Shariat, S.F.; Karakiewicz, P.I.; Godoy, G.; Karam, J.A.; Ashfaq, R.; Fradet, Y.; Isbarn, H.; Montorsi, F.; Jeldres, C.; Bastian, P.J.; Nielsen, M.E.; Müller, S.C.; Sagalowsky, A.I.; Lotan, Y. Survivin as a prognostic marker for urothelial carcinoma of the bladder: a multicenter external validation study. Clin. Cancer Res., 2009, 15(22), 7012-7019.
[] [PMID: 19903782]
Folkman, J.; Klagsbrun, M. Angiogenic factors. Science, 1987, 235(4787), 442-447.
[] [PMID: 2432664]
Jaeger, T.M.; Weidner, N.; Chew, K.; Moore, D.H.; Kerschmann, R.L.; Waldman, F.M.; Carroll, P.R. Tumor angiogenesis correlates with lymph node metastases in invasive bladder cancer. J. Urol., 1995, 154(1), 69-71.
[] [PMID: 7539869]
Korkolopoulou, P.; Konstantinidou, A.E.; Kavantzas, N.; Patsouris, E.; Pavlopoulos, P.M.; Christodoulou, P.; Thomas-Tsagli, E.; Davaris, P. Morphometric microvascular characteristics predict prognosis in superficial and invasive bladder cancer. Virchows Arch., 2001, 438(6), 603-611.
[] [PMID: 11469693]
Reiher, F.; Ozer, O.; Pins, M.; Jovanovic, B.D.; Eggener, S.; Campbell, S.C. p53 and microvessel density in primary resection specimens of superficial bladder cancer. J. Urol., 2002, 167(3), 1469-1474.
[] [PMID: 11832772]
Goddard, J.C.; Sutton, C.D.; Furness, P.N.; O’Byrne, K.J.; Kockelbergh, R.C. Microvessel density at presentation predicts subsequent muscle invasion in superficial bladder cancer. Clin. Cancer Res., 2003, 9(7), 2583-2586.
[PMID: 12855634]
Ajili, F.; Kacem, M.; Tounsi, H.; Darouiche, A.; Enayfer, E.; Chebi, M.; Manai, M.; Boubaker, S. Prognostic impact of angiogenesis in nonmuscle invasive bladder cancer as defined by microvessel density after immunohistochemical staining for CD34. Ultrastruct. Pathol., 2012, 36(5), 336-342.
[] [PMID: 22574784]
Dinney, C.P.; Babkowski, R.C.; Antelo, M.; Perrotte, P.; Liebert, M.; Zhang, H.Z.; Palmer, J.; Veltri, R.W.; Katz, R.L.; Grossman, H.B. Relationship among cystectomy, microvessel density and prognosis in stage T1 transitional cell carcinoma of the bladder. J. Urol., 1998, 160(4), 1285-1290.
[] [PMID: 9751337]
Bochner, B.H.; Cote, R.J.; Weidner, N.; Groshen, S.; Chen, S.C.; Skinner, D.G.; Nichols, P.W. Angiogenesis in bladder cancer: relationship between microvessel density and tumor prognosis. J. Natl. Cancer Inst., 1995, 87(21), 1603-1612.
[] [PMID: 7563203]
Inoue, K.; Slaton, J.W.; Karashima, T.; Yoshikawa, C.; Shuin, T.; Sweeney, P.; Millikan, R.; Dinney, C.P. The prognostic value of angiogenesis factor expression for predicting recurrence and metastasis of bladder cancer after neoadjuvant chemotherapy and radical cystectomy. Clin. Cancer Res., 2000, 6(12), 4866-4873.
[PMID: 11156246]
Huang, J.; Ma, X.; Chen, X.; Liu, X.; Zhang, B.; Minmin, L.; Nie, W.; Zhang, L.; Liu, L. Microvessel density as a prognostic factor in bladder cancer: a systematic review of literature and meta-analysis. Cancer Biomark., 2014, 14(6), 505-514.
[] [PMID: 25335742]
Dameron, K.M.; Volpert, O.V.; Tainsky, M.A.; Bouck, N. Control of angiogenesis in fibroblasts by p53 regulation of thrombospondin-1. Science, 1994, 265(5178), 1582-1584.
[] [PMID: 7521539]
Ioachim, E.; Michael, M.C.; Salmas, M.; Damala, K.; Tsanou, E.; Michael, M.M.; Malamou-Mitsi, V.; Stavropoulos, N.E. Thrombospondin-1 expression in urothelial carcinoma: prognostic significance and association with p53 alterations, tumour angiogenesis and extracellular matrix components. BMC Cancer, 2006, 6, 140.
[] [PMID: 16732887]
Shariat, S.F.; Youssef, R.F.; Gupta, A.; Chade, D.C.; Karakiewicz, P.I.; Isbarn, H.; Jeldres, C.; Sagalowsky, A.I.; Ashfaq, R.; Lotan, Y. Association of angiogenesis related markers with bladder cancer outcomes and other molecular markers. J. Urol., 2010, 183(5), 1744-1750.
[] [PMID: 20299037]
Goddard, J.C.; Sutton, C.D.; Jones, J.L.; O’Byrne, K.J.; Kockelbergh, R.C. Reduced thrombospondin-1 at presentation predicts disease progression in superficial bladder cancer. Eur. Urol., 2002, 42(5), 464-468.
[] [PMID: 12429155]
Grossfeld, G.D.; Ginsberg, D.A.; Stein, J.P.; Bochner, B.H.; Esrig, D.; Groshen, S.; Dunn, M.; Nichols, P.W.; Taylor, C.R.; Skinner, D.G.; Cote, R.J. Thrombospondin-1 expression in bladder cancer: association with p53 alterations, tumor angiogenesis, and tumor progression. J. Natl. Cancer Inst., 1997, 89(3), 219-227.
[] [PMID: 9017002]
Zu, X.; Tang, Z.; Li, Y.; Gao, N.; Ding, J.; Qi, L. Vascular endothelial growth factor-C expression in bladder transitional cell cancer and its relationship to lymph node metastasis. BJU Int., 2006, 98(5), 1090-1093.
[] [PMID: 17034609]
Miyata, Y.; Kanda, S.; Ohba, K.; Nomata, K.; Hayashida, Y.; Eguchi, J.; Hayashi, T.; Kanetake, H. Lymphangiogenesis and angiogenesis in bladder cancer: prognostic implications and regulation by vascular endothelial growth factors-A, -C, and -D. Clin. Cancer Res., 2006, 12(3 Pt 1), 800-806.
[] [PMID: 16467091]
Puntoni, M.; Petrera, M.; Campora, S.; Garrone, E.; Defferrari, C.; Torrisi, R. Torrisi, R prognostic significance of vegf after twenty year follow-up in a randomized trial of fenretinide in non-muscle invasive bladder cancer. Cancer Prev. Res. (Phila.), 2016.
Li, Z.; Qi, F.; Qi, L.; Zhang, H.; Chen, M.; Wang, L.; Zu, X. VEGF-C as a decision-making biomarker for selected patients with invasive bladder cancer who underwent bladder-preserving radical surgery. Arch. Med. Res., 2011, 42(5), 405-411.
[] [PMID: 21821075]
Lautenschlaeger, T.; George, A.; Klimowicz, A.C.; Efstathiou, J.A.; Wu, C.L.; Sandler, H.; Shipley, W.U.; Tester, W.J.; Hagan, M.P.; Magliocco, A.M.; Chakravarti, A. Bladder preservation therapy for muscle-invading bladder cancers on Radiation Therapy Oncology Group trials 8802, 8903, 9506, and 9706: vascular endothelial growth factor B overexpression predicts for increased distant metastasis and shorter survival. Oncologist, 2013, 18(6), 685-686.
[] [PMID: 23728940]
Huang, Y.J.; Qi, W.X.; He, A.N.; Sun, Y.J.; Shen, Z.; Yao, Y. Prognostic value of tissue vascular endothelial growth factor expression in bladder cancer: a meta-analysis. Asian Pac. J. Cancer Prev., 2013, 14(2), 645-649.
[] [PMID: 23621212]
Ogura, Y.; Sato, K.; Kato, T.; Saito, K.; Enomoto, K. [Immunohistochemical analysis of expression of angiogenic factors and tumor angiogenesis in superficial bladder cancer]. Nippon Hinyokika Gakkai Zasshi, 1998, 89(5), 529-537.
[] [PMID: 9642990]
Neal, D.E.; Sharples, L.; Smith, K.; Fennelly, J.; Hall, R.R.; Harris, A.L. The epidermal growth factor receptor and the prognosis of bladder cancer. Cancer, 1990, 65(7), 1619-1625.
[<1619::AID-CNCR2820650728>3.0.CO;2-Q] [PMID: 2311071]
Mellon, K.; Wright, C.; Kelly, P.; Horne, C.H.; Neal, D.E. Long term outcome related to epidermal growth factor receptor status in bladder cancer. J. Urol., 1995, 153(3 Pt 2), 919-925.
[] [PMID: 7853575]
Lipponen, P.; Eskelinen, M. Expression of epidermal growth factor receptor in bladder cancer as related to established prognostic factors, oncoprotein (c-erbB-2, p53) expression and long-term prognosis. Br. J. Cancer, 1994, 69(6), 1120-1125.
[] [PMID: 7911031]
Chakravarti, A.; Winter, K.; Wu, C.L.; Kaufman, D.; Hammond, E.; Parliament, M.; Tester, W.; Hagan, M.; Grignon, D.; Heney, N.; Pollack, A.; Sandler, H.; Shipley, W. Expression of the epidermal growth factor receptor and Her-2 are predictors of favorable outcome and reduced complete response rates, respectively, in patients with muscle-invading bladder cancers treated by concurrent radiation and cisplatin-based chemotherapy: a report from the Radiation Therapy Oncology Group. Int. J. Radiat. Oncol. Biol. Phys., 2005, 62(2), 309-317.
[] [PMID: 15890569]
Colquhoun, A.J.; Sundar, S.; Rajjayabun, P.H.; Griffiths, T.R.; Symonds, R.P.; Mellon, J.K. Epidermal growth factor receptor status predicts local response to radical radiotherapy in muscle-invasive bladder cancer. Clin. Oncol. (R. Coll. Radiol.), 2006, 18(9), 702-709.
[] [PMID: 17100158]
Pruthi, R.S.; Nielsen, M.; Heathcote, S.; Wallen, E.M.; Rathmell, W.K.; Godley, P.; Whang, Y.; Fielding, J.; Schultz, H.; Grigson, G.; Smith, A.; Kim, W. A phase II trial of neoadjuvant erlotinib in patients with muscle-invasive bladder cancer undergoing radical cystectomy: clinical and pathological results. BJU Int., 2010, 106(3), 349-354.
[] [PMID: 20089114]
Kassouf, W.; Luongo, T.; Brown, G.; Adam, L.; Dinney, C.P. Schedule dependent efficacy of gefitinib and docetaxel for bladder cancer. J. Urol., 2006, 176(2), 787-792.
[] [PMID: 16813948]
Philips, G.K.; Halabi, S.; Sanford, B.L.; Bajorin, D.; Small, E.J. A phase II trial of cisplatin (C), gemcitabine (G) and gefitinib for advanced urothelial tract carcinoma: results of Cancer and Leukemia Group B (CALGB) 90102. Ann. Oncol., 2009, 20(6), 1074-1079.
[] [PMID: 19168670]
Knowles, M.A. Role of FGFR3 in urothelial cell carcinoma: biomarker and potential therapeutic target. World J. Urol., 2007, 25(6), 581-593.
[] [PMID: 17912529]
Zieger, K.; Dyrskjøt, L.; Wiuf, C.; Jensen, J.L.; Andersen, C.L.; Jensen, K.M.; Ørntoft, T.F. Role of activating fibroblast growth factor receptor 3 mutations in the development of bladder tumors. Clin. Cancer Res., 2005, 11(21), 7709-7719.
[] [PMID: 16278391]
Maeng, Y.H.; Eun, S.Y.; Huh, J.S. Expression of fibroblast growth factor receptor 3 in the recurrence of non-muscle-invasive urothelial carcinoma of the bladder. Korean J. Urol., 2010, 51(2), 94-100.
[] [PMID: 20414420]
Bertz, S.; Abeé, C.; Schwarz-Furlan, S.; Alfer, J.; Hofstädter, F.; Stoehr, R.; Hartmann, A.; Gaumann, A.K. Increased angiogenesis and FGFR protein expression indicate a favourable prognosis in bladder cancer. Virchows Arch., 2014, 465(6), 687-695.
[] [PMID: 25326864]
Bahleda, R.; Dienstmann, R.; Adamo, B.; Gazzah, A.; Infante, J. Zhong, B Phase 1 study of JNJ-42756493, a pan-fibroblast growth factor receptor (FGFR) inhibitor, in patients with advanced solid tumors. J. Clin. Oncol., 2014, 32.
Burstein, H.J.; Temin, S.; Anderson, H.; Buchholz, T.A.; Davidson, N.E.; Gelmon, K.E.; Giordano, S.H.; Hudis, C.A.; Rowden, D.; Solky, A.J.; Stearns, V.; Winer, E.P.; Griggs, J.J. Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: american society of clinical oncology clinical practice guideline focused update. J. Clin. Oncol., 2014, 32(21), 2255-2269.
[] [PMID: 24868023]
Antonarakis, E.S.; Lu, C.; Wang, H.; Luber, B.; Nakazawa, M.; Roeser, J.C.; Chen, Y.; Mohammad, T.A.; Chen, Y.; Fedor, H.L.; Lotan, T.L.; Zheng, Q.; De Marzo, A.M.; Isaacs, J.T.; Isaacs, W.B.; Nadal, R.; Paller, C.J.; Denmeade, S.R.; Carducci, M.A.; Eisenberger, M.A.; Luo, J. AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N. Engl. J. Med., 2014, 371(11), 1028-1038.
[] [PMID: 25184630]
Krabbe, L.M.; Svatek, R.S.; Shariat, S.F.; Messing, E.; Lotan, Y. Bladder cancer risk: Use of the PLCO and NLST to identify a suitable screening cohort. Urol. Oncol., 2015, 33(65), e19-25.
Olsson, H.; Fyhr, I.M.; Hultman, P.; Jahnson, S. HER2 status in primary stage T1 urothelial cell carcinoma of the urinary bladder. Scand. J. Urol. Nephrol., 2012, 46(2), 102-107.
[] [PMID: 22150625]
Enache, M.; Simionescu, C.E.; Stepan, A. EGFR and Her2/neu immunoexpression in papillary urothelial bladder carcinomas. Rom. J. Morphol. Embryol., 2013, 54(1), 137-141.
[PMID: 23529321]
Janane, A.; Hajji, F.; Ismail, T.O.; Elondo, J.C.; Ghadouane, M.; Ameur, A.; Abbar, M.; Bouzidi, A. [Evaluation of HER2 protein overexpression in non-muscle-invasive bladder cancer with emphasis on tumour grade and recurrence]. Actas Urol. Esp., 2011, 35(4), 189-194.
[] [PMID: 21419519]
Lim, S.D.; Cho, Y.M.; Choi, G.S.; Park, H.K.; Paick, S.H.; Kim, W.Y.; Kim, S.N.; Yoon, G. Clinical significance of Substaging and HER2 expression in papillary nonmuscle invasive urothelial cancers of the urinary bladder. J. Korean Med. Sci., 2015, 30(8), 1068-1077.
[] [PMID: 26240484]
Chen, P.C.; Yu, H.J.; Chang, Y.H.; Pan, C.C. Her2 amplification distinguishes a subset of non-muscle-invasive bladder cancers with a high risk of progression. J. Clin. Pathol., 2013, 66(2), 113-119.
[] [PMID: 23087329]
Chow, N.H.; Chan, S.H.; Tzai, T.S.; Ho, C.L.; Liu, H.S. Expression profiles of ErbB family receptors and prognosis in primary transitional cell carcinoma of the urinary bladder. Clin. Cancer Res., 2001, 7(7), 1957-1962.
[PMID: 11448910]
Gandour-Edwards, R.; Lara, P.N., Jr; Folkins, A.K.; LaSalle, J.M.; Beckett, L.; Li, Y.; Meyers, F.J.; DeVere-White, R. Does HER2/neu expression provide prognostic information in patients with advanced urothelial carcinoma? Cancer, 2002, 95(5), 1009-1015.
[] [PMID: 12209684]
Jimenez, R.E.; Hussain, M.; Bianco, F.J., Jr; Vaishampayan, U.; Tabazcka, P.; Sakr, W.A.; Pontes, J.E.; Wood, D.P., Jr; Grignon, D.J. Her-2/neu overexpression in muscle-invasive urothelial carcinoma of the bladder: prognostic significance and comparative analysis in primary and metastatic tumors. Clin. Cancer Res., 2001, 7(8), 2440-2447.
[PMID: 11489824]
Kassouf, W.; Black, P.C.; Tuziak, T.; Bondaruk, J.; Lee, S.; Brown, G.A.; Adam, L.; Wei, C.; Baggerly, K.; Bar-Eli, M.; McConkey, D.; Czerniak, B.; Dinney, C.P. Distinctive expression pattern of ErbB family receptors signifies an aggressive variant of bladder cancer. J. Urol., 2008, 179(1), 353-358.
[] [PMID: 18006009]
Liedberg, F.; Anderson, H.; Chebil, G.; Gudjonsson, S.; Höglund, M.; Lindgren, D.; Lundberg, L.M.; Lövgren, K.; Fernö, M.; Månsson, W. Tissue microarray based analysis of prognostic markers in invasive bladder cancer: much effort to no avail? Urol. Oncol., 2008, 26(1), 17-24.
[] [PMID: 18190825]
Mellon, J.K.; Lunec, J.; Wright, C.; Horne, C.H.; Kelly, P.; Neal, D.E. C-erbB-2 in bladder cancer: molecular biology, correlation with epidermal growth factor receptors and prognostic value. J. Urol., 1996, 155(1), 321-326.
[] [PMID: 7490879]
Kolla, S.B.; Seth, A.; Singh, M.K.; Gupta, N.P.; Hemal, A.K.; Dogra, P.N.; Kumar, R. Prognostic significance of Her2/neu overexpression in patients with muscle invasive urinary bladder cancer treated with radical cystectomy. Int. Urol. Nephrol., 2008, 40(2), 321-327.
[] [PMID: 17899426]
Krüger, S.; Weitsch, G.; Büttner, H.; Matthiensen, A.; Böhmer, T.; Marquardt, T.; Sayk, F.; Feller, A.C.; Böhle, A. HER2 overexpression in muscle-invasive urothelial carcinoma of the bladder: prognostic implications. Int. J. Cancer, 2002, 102(5), 514-518.
[] [PMID: 12432555]
Sato, K.; Moriyama, M.; Mori, S.; Saito, M.; Watanuki, T.; Terada, K.; Okuhara, E.; Akiyama, T.; Toyoshima, K.; Yamamoto, T. An immunohistologic evaluation of C-erbB-2 gene product in patients with urinary bladder carcinoma. Cancer, 1992, 70(10), 2493-2498.
[<2493::AID-CNCR2820701017>3.0.CO;2-K] [PMID: 1358427]
Bolenz, C.; Shariat, S.F.; Karakiewicz, P.I.; Ashfaq, R.; Ho, R.; Sagalowsky, A.I.; Lotan, Y. Human epidermal growth factor receptor 2 expression status provides independent prognostic information in patients with urothelial carcinoma of the urinary bladder. BJU Int., 2010, 106(8), 1216-1222.
[] [PMID: 20089105]
Hussain, M.H.; MacVicar, G.R.; Petrylak, D.P.; Dunn, R.L.; Vaishampayan, U.; Lara, P.N., Jr; Chatta, G.S.; Nanus, D.M.; Glode, L.M.; Trump, D.L.; Chen, H.; Smith, D.C. Trastuzumab, paclitaxel, carboplatin, and gemcitabine in advanced human epidermal growth factor receptor-2/neu-positive urothelial carcinoma: results of a multicenter phase II National Cancer Institute trial. J. Clin. Oncol., 2007, 25(16), 2218-2224.
[] [PMID: 17538166]
Boorjian, S.; Ugras, S.; Mongan, N.P.; Gudas, L.J.; You, X.; Tickoo, S.K.; Scherr, D.S. Androgen receptor expression is inversely correlated with pathologic tumor stage in bladder cancer. Urology, 2004, 64(2), 383-388.
[] [PMID: 15302512]
Tuygun, C.; Kankaya, D.; Imamoglu, A.; Sertcelik, A.; Zengin, K.; Oktay, M.; Sertcelik, N. Sex-specific hormone receptors in urothelial carcinomas of the human urinary bladder: a comparative analysis of clinicopathological features and survival outcomes according to receptor expression. Urol. Oncol., 2011, 29(1), 43-51.
[] [PMID: 19372057]
Mir, C.; Shariat, S.F.; van der Kwast, T.H.; Ashfaq, R.; Lotan, Y.; Evans, A.; Skeldon, S.; Hanna, S.; Vajpeyi, R.; Kuk, C.; Alkhateeb, S.; Morote, J.; van Rhijn, B.W.; Bostrom, P.; Yao, J.; Miyamoto, H.; Jewett, M.; Fleshner, N.; Messing, E.; Zlotta, A.R. Loss of androgen receptor expression is not associated with pathological stage, grade, gender or outcome in bladder cancer: a large multi-institutional study. BJU Int., 2011, 108(1), 24-30.
[] [PMID: 21070579]
Nam, J.K.; Park, S.W.; Lee, S.D.; Chung, M.K. Prognostic value of sex-hormone receptor expression in non-muscle-invasive bladder cancer. Yonsei Med. J., 2014, 55(5), 1214-1221.
[] [PMID: 25048477]
Mashhadi, R.; Pourmand, G.; Kosari, F.; Mehrsai, A.; Salem, S.; Pourmand, M.R.; Alatab, S.; Khonsari, M.; Heydari, F.; Beladi, L.; Alizadeh, F. Role of steroid hormone receptors in formation and progression of bladder carcinoma: a case-control study. Urol. J., 2014, 11(6), 1968-1973.
[PMID: 25433476]
Izumi, K.; Ito, Y.; Miyamoto, H.; Miyoshi, Y.; Ota, J.; Moriyama, M.; Murai, T.; Hayashi, H.; Inayama, Y.; Ohashi, K.; Yao, M.; Uemura, H. Expression of androgen receptor in non-muscle-invasive bladder cancer predicts the preventive effect of androgen deprivation therapy on tumor recurrence. Oncotarget, 2016, 7(12), 14153-14160.
[] [PMID: 26885620]
Shen, S.S.; Smith, C.L.; Hsieh, J.T.; Yu, J.; Kim, I.Y.; Jian, W.; Sonpavde, G.; Ayala, G.E.; Younes, M.; Lerner, S.P. Expression of estrogen receptors-alpha and -beta in bladder cancer cell lines and human bladder tumor tissue. Cancer, 2006, 106(12), 2610-2616.
[] [PMID: 16700038]
Basakci, A.; Kirkali, Z.; Tuzel, E.; Yorukoglu, K.; Mungan, M.U.; Sade, M. Prognostic significance of estrogen receptor expression in superficial transitional cell carcinoma of the urinary bladder. Eur. Urol., 2002, 41(3), 342-345.
[] [PMID: 12180239]
Miyamoto, H.; Yao, J.L.; Chaux, A.; Zheng, Y.; Hsu, I.; Izumi, K.; Chang, C.; Messing, E.M.; Netto, G.J.; Yeh, S. Expression of androgen and oestrogen receptors and its prognostic significance in urothelial neoplasm of the urinary bladder. BJU Int., 2012, 109(11), 1716-1726.
[] [PMID: 22221549]
Tan, W.; Boorjian, S.; Advani, P.; Farmer, S.; Lohse, C.; Cheville, J.; Kwon, E.; Leibovich, B. The Estrogen Pathway: Estrogen Receptor-α, Progesterone Receptor, and Estrogen Receptor-β Expression in Radical Cystectomy Urothelial Cell Carcinoma Specimens. Clin. Genitourin. Cancer, 2015, 13(5), 476-484.
[] [PMID: 25981333]
Bolenz, C.; Lotan, Y.; Ashfaq, R.; Shariat, S.F. Estrogen and progesterone hormonal receptor expression in urothelial carcinoma of the bladder. Eur. Urol., 2009, 56(6), 1093-1095.
[] [PMID: 19596509]
Kauffman, E.C.; Robinson, B.D.; Downes, M.; Marcinkiewicz, K.; Vourganti, S.; Scherr, D.S.; Gudas, L.J.; Mongan, N.P. Estrogen receptor-β expression and pharmacological targeting in bladder cancer. Oncol. Rep., 2013, 30(1), 131-138.
[] [PMID: 23612777]
Wei, S.; Said-Al-Naief, N.; Hameed, O. Estrogen and progesterone receptor expression is not always specific for mammary and gynecologic carcinomas: a tissue microarray and pooled literature review study. Appl. Immunohistochem. Mol. Morphol., 2009, 17(5), 393-402.
[] [PMID: 19417624]
Hanahan, D.; Coussens, L.M. Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell, 2012, 21(3), 309-322.
[] [PMID: 22439926]
Fridman, W.H.; Pagès, F.; Sautès-Fridman, C.; Galon, J. The immune contexture in human tumours: impact on clinical outcome. Nat. Rev. Cancer, 2012, 12(4), 298-306.
[] [PMID: 22419253]
Sharma, P.; Shen, Y.; Wen, S.; Yamada, S.; Jungbluth, A.A.; Gnjatic, S.; Bajorin, D.F.; Reuter, V.E.; Herr, H.; Old, L.J.; Sato, E. CD8 tumor-infiltrating lymphocytes are predictive of survival in muscle-invasive urothelial carcinoma. Proc. Natl. Acad. Sci. USA, 2007, 104(10), 3967-3972.
[] [PMID: 17360461]
Winerdal, M.E.; Marits, P.; Winerdal, M.; Hasan, M.; Rosenblatt, R.; Tolf, A.; Selling, K.; Sherif, A.; Winqvist, O. FOXP3 and survival in urinary bladder cancer. BJU Int., 2011, 108(10), 1672-1678.
[] [PMID: 21244603]
Otto, W.; Denzinger, S.; Wieland, W.F.; Hartmann, A. First analysis of immune cell infiltration in stage pT1 urothelial bladder carcinoma: CD3 positivity as a prognostic marker for cancer-specific survival. World J. Urol., 2012, 30(6), 875-877.
[] [PMID: 23097035]
Patschan, O.; Sjödahl, G.; Chebil, G.; Lövgren, K.; Lauss, M.; Gudjonsson, S.; Kollberg, P.; Eriksson, P.; Aine, M.; Månsson, W.; Fernö, M.; Liedberg, F.; Höglund, M. A Molecular Pathologic Framework for Risk Stratification of Stage T1 Urothelial Carcinoma. Eur. Urol., 2015, 68(5), 824-832.
[] [PMID: 25770486]
Krpina, K.; Babarović, E.; Dorđević, G.; Fuckar, Z.; Jonjić, N. The association between the recurrence of solitary non-muscle invasive bladder cancer and tumor infiltrating lymphocytes. Croat. Med. J., 2012, 53(6), 598-604.
[] [PMID: 23275325]
Sjödahl, G.; Lövgren, K.; Lauss, M.; Chebil, G.; Patschan, O.; Gudjonsson, S.; Månsson, W.; Fernö, M.; Leandersson, K.; Lindgren, D.; Liedberg, F.; Höglund, M. Infiltration of CD3+ and CD68+ cells in bladder cancer is subtype specific and affects the outcome of patients with muscle-invasive tumors. Urol. Oncol., 2014, 32(6), 791-797.
[] [PMID: 24794251]
Kitamura, H.; Torigoe, T.; Honma, I.; Sato, E.; Asanuma, H.; Hirohashi, Y.; Sato, N.; Tsukamoto, T. Effect of human leukocyte antigen class I expression of tumor cells on outcome of intravesical instillation of bacillus calmette-guerin immunotherapy for bladder cancer. Clin. Cancer Res., 2006, 12(15), 4641-4644.
[] [PMID: 16899613]
Faraj, SF.; Munari, E.; Guner, G.; Taube, J.; Anders, R.; Hicks, J. Assessment of tumoral PD-L1 expression and intratumoral CD8+ T cells in urothelial carcinoma. Urology, 2015, 85(703), e1-6.
Ayari, C.; LaRue, H.; Hovington, H.; Decobert, M.; Harel, F.; Bergeron, A.; Têtu, B.; Lacombe, L.; Fradet, Y. Bladder tumor infiltrating mature dendritic cells and macrophages as predictors of response to bacillus Calmette-Guérin immunotherapy. Eur. Urol., 2009, 55(6), 1386-1395.
[] [PMID: 19193487]
Ayari, C.; LaRue, H.; Hovington, H.; Caron, A.; Bergeron, A.; Têtu, B.; Fradet, V.; Fradet, Y. High level of mature tumor-infiltrating dendritic cells predicts progression to muscle invasion in bladder cancer. Hum. Pathol., 2013, 44(8), 1630-1637.
[] [PMID: 23574787]
Takayama, H.; Nishimura, K.; Tsujimura, A.; Nakai, Y.; Nakayama, M.; Aozasa, K.; Okuyama, A.; Nonomura, N. Increased infiltration of tumor associated macrophages is associated with poor prognosis of bladder carcinoma in situ after intravesical bacillus Calmette-Guerin instillation. J. Urol., 2009, 181(4), 1894-1900.
[] [PMID: 19237175]
Hanada, T.; Nakagawa, M.; Emoto, A.; Nomura, T.; Nasu, N.; Nomura, Y. Prognostic value of tumor-associated macrophage count in human bladder cancer. Int. J. Urol., 2000, 7(7), 263-269.
[] [PMID: 10910229]
Hori, S.; Nomura, T.; Sakaguchi, S. Control of regulatory T cell development by the transcription factor Foxp3. Science, 2003, 299(5609), 1057-1061.
[] [PMID: 12522256]
Horn, T.; Laus, J.; Seitz, A.K.; Maurer, T.; Schmid, S.C.; Wolf, P.; Haller, B.; Winkler, M.; Retz, M.; Nawroth, R.; Gschwend, J.E.; Kübler, H.R.; Slotta-Huspenina, J. The prognostic effect of tumour-infiltrating lymphocytic subpopulations in bladder cancer. World J. Urol., 2016, 34(2), 181-187.
[] [PMID: 26055646]
Chemnitz, J.M.; Parry, R.V.; Nichols, K.E.; June, C.H.; Riley, J.L. SHP-1 and SHP-2 associate with immunoreceptor tyrosine-based switch motif of programmed death 1 upon primary human T cell stimulation, but only receptor ligation prevents T cell activation. J. Immunol., 2004, 173(2), 945-954.
[] [PMID: 15240681]
Topalian, S.L.; Sznol, M.; McDermott, D.F.; Kluger, H.M.; Carvajal, R.D.; Sharfman, W.H.; Brahmer, J.R.; Lawrence, D.P.; Atkins, M.B.; Powderly, J.D.; Leming, P.D.; Lipson, E.J.; Puzanov, I.; Smith, D.C.; Taube, J.M.; Wigginton, J.M.; Kollia, G.D.; Gupta, A.; Pardoll, D.M.; Sosman, J.A.; Hodi, F.S. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J. Clin. Oncol., 2014, 32(10), 1020-1030.
[] [PMID: 24590637]
Nakanishi, J.; Wada, Y.; Matsumoto, K.; Azuma, M.; Kikuchi, K.; Ueda, S. Overexpression of B7-H1 (PD-L1) significantly associates with tumor grade and postoperative prognosis in human urothelial cancers. Cancer Immunol. Immunother., 2007, 56(8), 1173-1182.
[] [PMID: 17186290]
Inman, B.A.; Sebo, T.J.; Frigola, X.; Dong, H.; Bergstralh, E.J.; Frank, I.; Fradet, Y.; Lacombe, L.; Kwon, E.D. PD-L1 (B7-H1) expression by urothelial carcinoma of the bladder and BCG-induced granulomata: associations with localized stage progression. Cancer, 2007, 109(8), 1499-1505.
[] [PMID: 17340590]
Boorjian, S.A.; Sheinin, Y.; Crispen, P.L.; Farmer, S.A.; Lohse, C.M.; Kuntz, S.M.; Leibovich, B.C.; Kwon, E.D.; Frank, I. T-cell coregulatory molecule expression in urothelial cell carcinoma: clinicopathologic correlations and association with survival. Clin. Cancer Res., 2008, 14(15), 4800-4808.
[] [PMID: 18676751]
Xylinas, E.; Robinson, B.D.; Kluth, L.A.; Volkmer, B.G.; Hautmann, R.; Küfer, R.; Zerbib, M.; Kwon, E.; Thompson, R.H.; Boorjian, S.A.; Shariat, S.F. Association of T-cell co-regulatory protein expression with clinical outcomes following radical cystectomy for urothelial carcinoma of the bladder. Eur. J. Surg. Oncol., 2014, 40(1), 121-127.
[] [PMID: 24140000]
Bellmunt, J.; Mullane, S.A.; Werner, L.; Fay, A.P.; Callea, M.; Leow, J.J.; Taplin, M.E.; Choueiri, T.K.; Hodi, F.S.; Freeman, G.J.; Signoretti, S. Association of PD-L1 expression on tumor-infiltrating mononuclear cells and overall survival in patients with urothelial carcinoma. Ann. Oncol., 2015, 26(4), 812-817.
[] [PMID: 25600565]
Rosenberg, J.E.; Hoffman-Censits, J.; Powles, T.; van der Heijden, M.S.; Balar, A.V.; Necchi, A.; Dawson, N.; O’Donnell, P.H.; Balmanoukian, A.; Loriot, Y.; Srinivas, S.; Retz, M.M.; Grivas, P.; Joseph, R.W.; Galsky, M.D.; Fleming, M.T.; Petrylak, D.P.; Perez-Gracia, J.L.; Burris, H.A.; Castellano, D.; Canil, C.; Bellmunt, J.; Bajorin, D.; Nickles, D.; Bourgon, R.; Frampton, G.M.; Cui, N.; Mariathasan, S.; Abidoye, O.; Fine, G.D.; Dreicer, R. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet, 2016, 387(10031), 1909-1920.
[] [PMID: 26952546]
Shirahama, T. Cyclooxygenase-2 expression is up-regulated in transitional cell carcinoma and its preneoplastic lesions in the human urinary bladder. Clin. Cancer Res., 2000, 6(6), 2424-2430.
[PMID: 10873095]
Shariat, S.F.; Matsumoto, K.; Kim, J.; Ayala, G.E.; Zhou, J.H.; Jian, W.; Benedict, W.F.; Lerner, S. Correlation of cyclooxygenase-2 expression with molecular markers, pathological features and clinical outcome of transitional cell carcinoma of the bladder. J. Urol., 2003, 170(3), 985-989.
[] [PMID: 12913755]
Wadhwa, P.; Goswami, A.K.; Joshi, K.; Sharma, S.K. Cyclooxygenase-2 expression increases with the stage and grade in transitional cell carcinoma of the urinary bladder. Int. Urol. Nephrol., 2005, 37(1), 47-53.
[] [PMID: 16132759]
Youssef, R.; Kapur, P.; Kabbani, W.; Shariat, S.F.; Mosbah, A.; Abol-Enein, H.; Ghoniem, M.; Lotan, Y. Bilharzial vs non-bilharzial related bladder cancer: pathological characteristics and value of cyclooxygenase-2 expression. BJU Int., 2011, 108(1), 31-37.
[] [PMID: 21105986]
Friedrich, M.G.; Toma, M.I.; Petri, S.; Huland, H. Cyclooxygenase-2 promotes angiogenesis in pTa/T1 urothelial bladder carcinoma but does not predict recurrence. BJU Int., 2003, 92(4), 389-392.
[] [PMID: 12930427]
Diamantopoulou, K.; Lazaris, A.; Mylona, E.; Zervas, A.; Stravodimos, K.; Nikolaou, I.; Athanassiadou, S.; Nakopoulou, L. Cyclooxygenase-2 protein expression in relation to apoptotic potential and its prognostic significance in bladder urothelial carcinoma. Anticancer Res., 2005, 25(6C), 4543-4549.
[PMID: 16334139]
Kim, S.I.; Kwon, S.M.; Kim, Y.S.; Hong, S.J. Association of cyclooxygenase-2 expression with prognosis of stage T1 grade 3 bladder cancer. Urology, 2002, 60(5), 816-821.
[] [PMID: 12429306]
Shariat, S.F.; Kim, J.H.; Ayala, G.E.; Kho, K.; Wheeler, T.M.; Lerner, S.P. Cyclooxygenase-2 is highly expressed in carcinoma in situ and T1 transitional cell carcinoma of the bladder. J. Urol., 2003, 169(3), 938-942.
[] [PMID: 12576817]
Wülfing, C.; Eltze, E.; von Struensee, D.; Wülfing, P.; Hertle, L.; Piechota, H. Cyclooxygenase-2 expression in bladder cancer: correlation with poor outcome after chemotherapy. Eur. Urol., 2004, 45(1), 46-52.
[] [PMID: 14667515]
Aziz, A.; Lessard, A.; Moore, K.; Hovington, H.; Latulippe, E.; Larue, H.; Fradet, Y.; Lacombe, L. Improved cancer specific-survival in patients with carcinoma invading bladder muscle expressing cyclo-oxygenase-2. BJU Int., 2011, 108(4), 531-537.
[] [PMID: 21166751]
Shariat, S.F.; Passoni, N.; Bagrodia, A.; Rachakonda, V.; Xylinas, E.; Robinson, B.; Kapur, P.; Sagalowsky, A.I.; Lotan, Y. Prospective evaluation of a preoperative biomarker panel for prediction of upstaging at radical cystectomy. BJU Int., 2014, 113(1), 70-76.
[] [PMID: 24053584]

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2020
Published on: 23 July, 2020
Page: [1133 - 1152]
Pages: 20
DOI: 10.2174/1389557516666160512151202
Price: $65

Article Metrics

PDF: 24