title: DNA mismatch repair-related protein loss as a prognostic factor in endometrial cancers.
abstract: OBJECTIVE
  Recent investigations have revealed DNA mismatch repair (MMR) gene mutations are closely related with carcinogenesis of endometrial cancer; however the impact of MMR protein expression on prognosis is not determined. Correlations between MMR-related protein expression and clinicopathological factors of endometrial cancers are analyzed in the present study.
  
  
  METHODS
  A total of 191 endometrial cancer tissues treated between 1990 and 2007 in our hospital were enrolled. Immunoreactions for MSH2, MLH1, MSH6, and PMS2 on tissue microarray specimens and clinicopathological features were analyzed retrospectively.
  
  
  RESULTS
  Seventy-six cases (40%) had at least one immunohistochemical alteration in MMR proteins (MMR-deficient group). There were statistically significant differences of histology, International Federation of Gynecology and Obstetrics (FIGO) stage, and histological grade between MMR-deficient group and the other cases (MMR-retained group). Response rate of first-line chemotherapy in evaluable cases was slightly higher in MMR-deficient cases (67% vs. 44%, p=0.34). MMR-deficient cases had significantly better progression-free and overall survival (OS) compared with MMR-retained cases. Multivariate analysis revealed MMR status was an independent prognostic factor for OS in endometrial cancers.
  
  
  CONCLUSIONS
  MMR-related proteins expression was identified as an independent prognostic factor for OS, suggesting that MMR was a key biomarker for further investigations of endometrial cancers.
authors.affiliation: Department of Obstetrics and Gynecology, National Defense Medical College Hospital, Tokorozawa, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kato
authors.affiliation: Department of Obstetrics and Gynecology, National Defense Medical College Hospital, Tokorozawa, Japan. mastkn@ndmc.ac.jp.
authors.forename: Masashi
authors.initials: M
authors.lastname: Takano
authors.affiliation: Department of Obstetrics and Gynecology, National Defense Medical College Hospital, Tokorozawa, Japan.
authors.forename: Morikazu
authors.initials: M
authors.lastname: Miyamoto
authors.affiliation: Department of Obstetrics and Gynecology, National Defense Medical College Hospital, Tokorozawa, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Sasaki
authors.affiliation: Department of Obstetrics and Gynecology, National Defense Medical College Hospital, Tokorozawa, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Goto
authors.affiliation: Department of Basic Pathology, National Defense Medical College Hospital, Tokorozawa, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsuda
authors.affiliation: Department of Obstetrics and Gynecology, National Defense Medical College Hospital, Tokorozawa, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Furuya
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000172:deficiency / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D053843:DNA Mismatch Repair; D045643:DNA Repair Enzymes / Q000172:deficiency / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000378:metabolism*; D016889:Endometrial Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000172:deficiency / Q000378:metabolism; D009363:Neoplasm Proteins / Q000172:deficiency / Q000378:metabolism; D009687:Nuclear Proteins / Q000172:deficiency / Q000378:metabolism; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; C497172:MSH2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes
keywords: Biological Markers; Carcinogenesis; DNA Mismatch Repair; Endometrial Neoplasms; Multivariate Analysis; Retrospective Studies