Immunohistochemical analysis of DNA 'mismatch-repair' enzyme human Mut-S-Homologon-2 in ovarian carcinomas

The human Mut-S-Homologon-2 (hMSH-2) gene product is a member of a highly c onserved family of proteins involved in postreplication mismatch repair. We have analysed hMSH-2 expression in normal ovarian tissue (n = 15) and ovar ian carcinomas (n = 40). hMSH-2 protein was investigated immunohistochemica lly on frozen sections using a highly sensitive streptavidin-peroxidase tec hnique and a specific mouse monoclonal antibody (clone FE11). A hMSH-2-immu noreactivity score (hMSH-2-IRS) for semiquantitative analysis of hMSH-2 exp ression is presented. In normal ovarian tissue, we only found weak nuclear immunoreactivity for hMSH-2 in 60%, while the remaining 40% were hMSH-2 neg ative (mean hMSH-2-IRS: 0.73; SD: +/- 0.70). All ovarian carcinomas analyse d revealed moderate to strong nuclear immunoreactivity (mean hMSH-2-IRS: 8. 05; SD: +/- 3.65). hMSH-2 staining was heterogeneous, with visual differenc es between individual tumour cells. Expression of hMSH-2 protein was consis tently and strongly upregulated in tumour cells of ovarian carcinomas as co mpared to normal ovarian tissue. No statistically significant correlation i n comparing the labelling patterns for hMSH-2 with the labelling patterns f or Ki-67 (mean percentage of Ki-67 positive tumour cells: 25.88%; SD: +/- 1 8.43) was observed in ovarian carcinomas. Furthermore, no statistical signi ficant correlations between hMSH-2-IRS and histological grading (p = 0.47), histological type of carcinoma (p = 0.706) or FIGO-classification (p = 0.0 54) were found. Our findings indicate that (a) hMSH-2 is expressed in norma l human ovarian tissue, (b) expression of hMSH-2 is increased in ovarian ca rcinomas, (c) expression of hMSH-2 may be of importance for the genetic sta bility of ovarian carcinomas in vivo, (d) hMSH-2 mutations may not cause mi crosatellite instability in ovarian carcinomas, (e) hMSH-2 may contribute t o mechanisms responsible for resistance to anticancer drugs.