The Role of CXC-Chemokine IL-8, IL-6 and CXCR2 Receptor in Lymphoplasmacytic Lymphoma: Correlations with Microvascular Characteristics and Clinical Features
Georgia Levidou, Tatiana Tzenou, Marie-Christine Kyrtsonis, Eftychia Nikolaou, Nikolaos Kavantzas, Dimitris Maltezas, Katerina Xirokosta, Efstathios Koulieris, Athanasia Sepsa, Katerina Bitsanis, Ilias Pessach, Vassiliki Bartzis, Maria Dimou, Panayiotis Panayiotidis, Gerassimos A Pangalis, Efstratios Patsouris and Penelope Korkolopoulou
Affiliation: First Department of Pathology, Laikon Hospital, University of Athens, Medical School 11527 Athens, Greece.
Neovascularisation is a vital process underlying the development and progression of malignant neoplasms.
Limited information on the subject is available regarding Waldenstrom’s macroglobulinemia/Lymphoplasmacytic lymphoma
(WM/LPL), a rare and usually indolent B-cell lymphoma. We therefore studied by immunohistochemistry microvessel
characteristics and IL-6, IL-8, CXCR2 and VEGF expression in the bone marrow of WM/LPL patients and investigated
any possible correlation with disease characteristics and outcome. Sixty-three patients were studied (47 WM
and 16 LPL) of whom 32, 25 and 6 were low, intermediate and high risk respectively, according to the IPSSWM staging
system. Seventy-six percent of the patients required treatment while 24% were asymptomatic and were regularly followed-
up. Microvascular characteristics, i.e microvessel density (MVD), total vascular area (TVA) and several other sizeand
shape-related parameters, were evaluated in CD34-stained bone marrow slides using computerized image analysis. A
Histo-score (H-score) was calculated for IL-6, IL-8, CXCR2 and VEGF expression. IL-6, IL-8, IL-8 receptor CXCR2 and
VEGF expression was observed in 84%, 43%, 89% and 90% respectively. A positive correlation between IL-6 and
CXCR2 H-scores was observed; IL-6 and VEGF H-scores correlated with hypoalbulinemia and increased serum β2-
microglobulin respectively and both with bone marrow lymphoplasmacytic infiltration and MVD. The degree of angiogenesis,
microvessel shape, VEGF expression and CXCR2 expression correlated with a shorter time to first treatment in
multivariate analysis. In conclusion, in WM/LPL, increased expression of Th-2 cytokines, CXCR2 and VEGF is implicated
in neovascularization. CXCR2 and VEGF expression along with the extent and the architecture of the microvessels
are brought forward as contributors to biologic aggressiveness reflected by a need for earlier treatment.
Keywords: Angiogenesis, CD34, CXCR2, IL-6, IL-8, lymphoplasmacytic lymphoma, pathophysiology, prognosis, VEGF,
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