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 development of various human cancers including sporadic endometrial cancer and is characterized by length changes at repetitive loci scattered throughout the genome. It has been shown that cancer predisposition is attributable to defects in any one of four genes, all of which encode homologs of the microbial mismatch repair proteins mutS and mutL. The human Mut-S-Homologon-2 gene (hMSH-2) specifies a mutS homolog, whereas hMLH-1, hPMS-1 and hPMS-2 encode homologs of mutL.


METHODS
Freshly excised endometrial specimens (malignancies of 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 tissues were human Mut-S-Homologon-2 negative, while the remaining 75% revealed weak 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 Mut-S-Homologon-2-IRS: 9.12, SD: +/-3.34; mean human Mut-S-Homologon-2-PP: 81.82, SD: +/-15.67; mean human Mut-S-Homologon-2-IS: 2.58, SD: +/-0.71). In addition, expression of human Mut-S-Homologon-2 protein was statistically significantly upregulated in tumor cells of malignancies of the uterine corpus as compared to normal endometrial tissue on the 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 consistently increased in endometrial neoplasms compared to normal endometrial tissue.


CONCLUSIONS
The expression of the human MUT-S-Homologon-2 is increased both on the protein- and on mRNA-level in endometrial neoplasms compared to normal endometrial tissue possibly caused by the neoplastic process driven by an increase in the rate of mutations in oncogenes and tumor suppressor genes.
Friedrich
M
M
Department of Obstetrics and Gynecology, University of Saarland, Homburg/Saar, Germany.
D004260:DNA Repair; D004268:DNA-Binding Proteins; D016889:Endometrial Neoplasms / Q000737:chemistry* / Q000235:genetics; D004717:Endometrium / Q000737:chemistry; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051718:MutS Homolog 2 Protein; D011518:Proto-Oncogene Proteins / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein