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 conserved family of proteins involved in postreplication mismatch repair. We have analysed hMSH-2 expression in normal ovarian tissue (n = 15) and ovarian carcinomas (n = 40). hMSH-2 protein was investigated immunohistochemically on frozen sections using a highly sensitive streptavidin-peroxidase technique and a specific mouse monoclonal antibody (clone FE11). A hMSH-2-immunoreactivity score (hMSH-2-IRS) for semiquantitative analysis of hMSH-2 expression is presented. In normal ovarian tissue, we only found weak nuclear immunoreactivity for hMSH-2 in 60%, while the remaining 40% were hMSH-2 negative (mean hMSH-2-IRS: 0.73; SD: +/-0.70). All ovarian carcinomas analysed revealed moderate to strong nuclear immunoreactivity (mean hMSH-2-IRS: 8.05; SD: +/-3.65). hMSH-2 staining was heterogeneous, with visual differences between individual tumour cells. Expression of hMSH-2 protein was consistently and strongly upregulated in tumour cells of ovarian carcinomas as compared to normal ovarian tissue. No statistically significant correlation in comparing the labelling patterns for hMSH-2 with the labelling patterns for Ki-67 (mean percentage of Ki-67 positive tumour cells: 25.88%; SD: +/-18.43) was observed in ovarian carcinomas. Furthermore, no statistical significant correlations between hMSH-2-IRS and histological grading (p = 0.47), histological type of carcinoma (p = 0.706) or FIGO-classification (p = 0.054) were found. Our findings indicate that (a) hMSH-2 is expressed in normal human ovarian tissue, (b) expression of hMSH-2 is increased in ovarian carcinomas, (c) expression of hMSH-2 may be of importance for the genetic stability of ovarian carcinomas in vivo, (d) hMSH-2 mutations may not cause microsatellite instability in ovarian carcinomas, (e) hMSH-2 may contribute to mechanisms responsible for resistance to anticancer drugs.
Friedrich
M
M
Department of Obstetrics and Gynecology, Universität des Saarlandes, Homburg/Saar, Germany.
Villena-Heinsen
C
C
Meyberg
R
R
Woll-Hermann
A
A
Reitnauer
K
K
Schmidt
W
W
Tilgen
W
W
Reichrath
J
J
D000230:Adenocarcinoma / Q000201:enzymology* / Q000473:pathology; D000818:Animals; D000911:Antibodies, Monoclonal; D020137:Base Pair Mismatch; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000032:analysis; D051379:Mice; D051718:MutS Homolog 2 Protein; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; C497173:Msh2 protein, mouse; D051718:MutS Homolog 2 Protein