Loss of hMLH1 expression correlates with improved survival in stage III-IV ovarian cancer patients.
Pre-clinical data suggest a relationship between DNA MisMatch Repair (MMR) system failure, particularly the inactivation of genes hMLH1 and hMSH2, and resistance to drugs like cisplatin and carboplatin. We studied the correlation between loss of hMLH1 expression in tumour cells and clinical outcome in 38 patients with ovarian cancer, who underwent cisplatin-based chemotherapy. 19 patients (56%) showed loss of hMLH1 expression (Group A) while 15 patients (44%) showed normal hMLH1 expression (Group B). 4 patients were not evaluable for hMLH1 expression. The 2 groups of patients were similar for clinical characteristics, response to chemotherapy and time to progression. Group A patients showed a median survival of 55 months whereas Group B patients had a median survival of 12 months (P=0.014). Loss of hMLH1 expression was the only independent predictor of survival in the multivariate analysis. Our observations suggest a relationship between loss of hMLH1 and improved survival in advanced ovarian cancer.
Department of Clinica di Oncologia Medica, Ospedale Regionale di Torrette, Via Conca, 60020 Ancona, Italy.
M
M
Scartozzi
M
M
De Nictolis
E
E
Galizia
P
P
Carassai
F
F
Bianchi
R
R
Berardi
R
R
Gesuita
A
A
Piga
R
R
Cellerino
E
E
Porfiri
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002352:Carrier Proteins; D002945:Cisplatin / Q000627:therapeutic use; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics*; D012044:Regression Analysis; D016019:Survival Analysis
D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1; D002945:Cisplatin