hMSH2 and GTBP expression in advanced stage epithelial ovarian cancer

Abstract

Summary Defects in DNA mismatch repair have been associated with both hereditary and sporadic forms of human cancer. Most of the attention has been focused on the incidence and genetics of mismatch repair defects, while little is known about the expression levels of the mismatch repair proteins and their significance in cancer cell biology. In this study, both the expression levels of hMSH2 and GTBP proteins were investigated by Western blotting in 20 untreated epithelial ovarian cancers. For these analyses, a commercial anti-hMSH2 monoclonal antibody and a newly generated mouse monoclonal anti-GTBP antibody were used. hMSH2 and GTBP proteins were detected by Western blotting in 19 out of 20 (95%) samples analysed and were found to be directly correlated (r = +0.51, P = 0.025). hMSH2 expression was significantly higher in ovarian cancer cells originating from solid tumours than from ascites (H = 4.5, P = 0.033), whereas GTBP content did not significantly differ according to the origin of cancer cells. No statistically significant differences were found in the distribution of hMSH2 and GTBP levels according to the age of the patients, grade of differentiation, histotype and extent of surgical debulking. The amount of hMSH2 protein was demonstrated to be significantly lower in stage IV than in stage III patients (H = 7.35, P = 0.007). Moreover, significantly lower hMSH2 levels were observed in non-responding patients compared to patients who achieved complete or partial response to cisplatin-based chemotherapy (H = 4.88, P = 0.027). Conversely, GTBP levels were not distributed differently according to stage of disease and chemotherapy response. Our study suggests a possible involvement of hMSH2 in ovarian cancer cell biology and susceptibility to chemotherapy. The possible biological and/or clinical role of GTBP expression in ovarian cancer patients remains to be elucidated.

Survival of Patients with Ovarian Cancer due to a Mismatch Repair Defect

“…Experimental studies have shown that mismatch repair deficient colon cell lines are tolerant to chemotherapy [16]. Other studies have suggested that also mismatch repair deficient OC cell lines are resistant to chemotherapy [17,18]. One case report supported these findings [19].…”

“…In vitro studies suggested an involvement of mismatch repair gene mutations in decreased susceptibility of ovarian cancer cells to cisplatin therapy [17,18]. Standard treatment of OC contains platinum agents.…”

Expression of DNA mismatch repair gene MSH2 in cytological material from lung cancer patients

“…5,6 Among these genes, MSH2 encodes for a DNA-mismatch repair protein that has been previously found to be altered in human solid tumors. [7][8][9] Considering that evaluation of MSH2 expression in cytological specimens has been reported only in metastatic to lymph nodes and liver melanomas, 10 in this study, we have analyzed by immunocytochemistry the expression of MSH2 DNA-repair protein in a bank of cytological material obtained by fine needle aspiration (FNA) from patients diagnosed with lung adenocarcinoma, small cell carcinoma, or squamous cell carcinoma.…”

Prevalence of Loss of Expression of DNA Mismatch Repair Proteins in Primary Epithelial Ovarian Tumors

“…Identifying epithelial ovarian tumors with MMR defects is not only important for early detection of women with Lynch syndrome, but may also have treatment implications. Several in-vitro studies and a small case series also suggest a relation between MMR gene mutations and decreased susceptibility to cisplatin, a common chemotherapeutic agent used to treat ovarian carcinomas (14)(15)(16)(17)(18). Several in-vitro studies and a small case series also suggest a relation between MMR gene mutations and decreased susceptibility to cisplatin, a common chemotherapeutic agent used to treat ovarian carcinomas (14)(15)(16)(17)(18).…”