title: Analysis of hMLH1 and hMSH2 expression in cisplatin-treated ovarian cancer patients.
abstract: BACKGROUND
  Loss of DNA mismatch repair may result in resistance to platinum- based anticancer drugs. The hMLH1 and hMSH2 proteins play a critical role in the maintenance of genome integrity and are involved in resistance to platinum-based therapy in colorectal cancer, which is deficient in hMLH1 protein and endometrial cancer, as well as in hMSH2 protein. However, the predictive value of MLH1 and MSH2 expression in ovarian cancer cisplatin-resistance is still to be determined.
  
  
  OBJECTIVE
  The aim of this study was to investigate the expression of hMLH1 and hMSH2 proteins in ovarian carcinoma specimens and to evaluate their prognostic significance by means of overall survival (OS) and progression-free survival rates (PSF).
  
  
  METHODS
  Ovarian cancer tissues were obtained from 61 patients: 45 platinum-sensitive and 16 platinum-resistant. hMLH1 and hMSH2 proteins expression was evaluated by immunohistochemistry, with the use of mouse monoclonal antibodies clone 14 for hMLH1 and clone FE11 for hMSH2. The log-rank test and Kaplan-Meier statistics were used to analyze the relationship between proteins expression and progression free survival, as well as the overall survival.
  
  
  RESULTS
  No significant correlation was found between hMLH1 and hMSH2 expression and overall survival and progression free survival in the group of patients sensitive and resistant to cisplatin. No significant difference was found in proteins expression intensity between the two compared groups of patients. Age of patients, type of cancer histology, FIGO staging, grading, clinical response and CA 125 did not reveal correlation with the expression of the analyzed proteins.
  
  
  CONCLUSIONS
  The immunohistochemical expression of hMLH1 and hMSH2 proteins in ovarian cancer has no predictive value in resistance to cisplatin.
authors.affiliation: Department of Gynecology, Obstetrics and Gynecologic Oncology, Division of Gynecologic Oncology, Poznan University of Medical Sciences, Polna.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Magnowska
authors.forename: Paweł
authors.initials: P
authors.lastname: Surowiak
authors.forename: Ewa
authors.initials: E
authors.lastname: Nowak-Markwitz
authors.forename: Marcin
authors.initials: M
authors.lastname: Michalak
authors.forename: Piotr
authors.initials: P
authors.lastname: Magnowski
authors.forename: Wojciech
authors.initials: W
authors.lastname: Rokita
authors.forename: Helena
authors.initials: H
authors.lastname: Kedzia
authors.forename: Maciej
authors.initials: M
authors.lastname: Zabel
authors.forename: Marek
authors.initials: M
authors.lastname: Spaczyński
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002945:Cisplatin / Q000627:therapeutic use*; D053843:DNA Mismatch Repair; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D011044:Poland; D016019:Survival Analysis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D002945:Cisplatin