Microsatellite Instability (MSI) as Genomic Marker in Endometrial Cancer: Toward Scientific Evidences

A.      Tinelli; V.      Mezzolla; G.      Leo; M.      Pisano; F.      Storelli; G.      Alemanno; A.      Malvasi; S.      Tommasi; G.      Ronzino; V.      Lorusso

Abstract

Endometrial Cancer is the most frequent tumor in western world nations, with 142,000 new cases each year and 42,000 casualties. This form of cancer typically affects women between 55 and 65 years of age, and ranks fourth among female tumors. Endogenous predisposing conditions to endometrial cancer development are: late menopause, early menarche and hyperestrogenism, while hormone replacement therapy, obesity, alcohol, diabetes, and a diet rich in animal fats as well as chronic liver disease, are the exogenous factors. This tumor may also have an hereditary predisposition, as in the Lynch Syndrome or in HNPCC (Hereditary NonPolyposis Colorectal Cancer), since genetic modifications induced by the “MisMatch Repair” genes lead to a tumoral development susceptibility, not only in the colon. The phenotypical consequences of these genetic modifications may be found in the microsatellite instability (MSI) and in the loss of heterozygosity (LOH), which generate the replication errors in positive phenotypes repeats. These express the incapability to repair short nucleotide insertions or deletions, generated by a wrong DNA replication. Due to such genetic modifications, new allelic variants arise in the endometrial tissue, confirming the high degree of this genetic disorder. Recent studies showed that the MSI and LOH in endometrial cells may be associated with the possible loss in the expression of cellular control and with the possible degeneration of the cell growth phenomenon. There is also a possibility of utilizing these new genetic markers in the endometrial mucosa to study these tissues and to detect any possible neoplastic transformations, thanks to Genomics.

Keywords: Endometrial cancer, microsatellite instability, MSI, HNPCC, endometrial hyperplasia, Lynch sindrome, genomics, proteomics, laparoscopy, endoscopy, Genomic Marker, tumors, menopause, hyperestrogenism, Lynch Syndrome, Hereditary NonPolyposis Colorectal Cancer, DNA replication, neoplastic transformations, gynecological cancers, malignant uterine cancers, uterine tumors, MisMatch Repair genes, MMR genes, replication errors in repeats, adenomas, Familiar Adenomatous Polyposis, breast cancer, National Cancer Institute, Tandem-repetitive DNA, satellite DNA, DNA profiling, Polymerase Chain Reaction, telomeres, Immunohistochemical analysis, Methylation analysis, DNA finger-printing, polymerase slippage, Neisseria gonorrhoeae, codone, frameshift, phase variation, Eukaryotes, X Fragile Syndrome, bromide ethydium, silver staining, poliacrylammide, fluorochromes, Neoplasms, candidate-linkage, oncosuppressor genes, TGF RII, human MutS homologue, Dinucleotide marker, deleted colorectal cancer gene