Analysis of the DNA "mismatch-repair" enzyme human Mut-S-Homologon-2 in endometrial cancer on protein- and RNA-level

Background: Microsatellite: instability seems to be important in the develo pment of various human cancers including sporadic endometrial cancer and is characterized by length changes at repetitive loci scattered throughout th e genome. It has been shown that cancer predisposition is attributable to d efects in any one of four genes, all of which encode homologs of the microb ial mismatch repair proteins mutS and mutL. The human Mut-S-Homologon-2 gen e (hMSH-2) specifies a mutS homolog, whereas hMLH-1, hPMS-1 anti hPMS-2 enc ode homologs of mutL. Material and Methods: Freshly excised endometrial specimens (malignancies o f the uterine corpus: n=50; normal endometrial tissue: n=20) were examined by immunohistochemistry (mAb FE 11, Dianova, Germany and RT-PCR to analyze the expression of human MUT-S-Homologon-2 on protein- and mRNA-level. Most of the neoplasms of the uterine corpus were sporadic endometrial. Results: In the immunohistochemical study, 25% of normal endometrial tissue s were human Mut-S-Homologon-2 negative, while the remaining 75% revealed w eak human Mut-S-Homologon-2 immunoreactivity (mean human Mut-S-Homologon-2 IRS: 1.52; SD: +/-1.42 mean human Mut-S-Homologon-2-PP: 12.12; SD: +/-10.31 ; mean human Mut-S-Homologon-2 IS: 0.98; SD: +/-0.81). All malignancies of the uterine corpus revealed strong nuclear immunoreactivity for human Mut-S -Homologon-2 (mean human MutS-Homologon-2-IRS: 9.12, SD: +/-3.34; mean huma n Mut-S-Homologon-2-PP: 81.82, SD: +/-15.67; mean human Mut-S-Homologon-2-I S: 2.58, SD: +/-0.71). In addition, expression of human Mut-S-Homologon-2 p rotein was statistically significantly upregulated in tumor cells of malign ancies of the uterine corpus as compared to normal endometrial tissue on th e protein level. In the: RT-PCR study, the hMSH-2 gene was highly expressed in endometrial neoplasms on the mRNA-level. hMSH-2 expression was consiste ntly increased in endometrial neoplasms compared to normal endometrial tiss ue. Conclusion: The expression of the human MUT-S-Homologon-2 is increased both on the protein- and on mRNA-level in endometrial neoplasms compared to nor mal endometrial tissue possibly caused by the neoplastic process driven by an increase in the rate of mutations in oncogenes and tumor suppressor gene s.