title: Impact of microsatellite instability (MSI) on survival in high grade endometrial carcinoma.
abstract: OBJECTIVE
  Although microstellite instability (MSI) is a prognostic marker in colorectal cancer, it's relation with prognosis in the endometrial cancer is controversial. The goal of this study is to identify the correlation between MSI and clinicopathologic markers along with survival in high grade endometrial carcinoma EC.
  
  
  METHODS
  Between 1995 and 2004, we identified 119 patients (57 type-I, and 62 type-II) diagnosed with high grade EC and underwent hysterectomy. Sections were immunostained using antibodies against MLH1, MSH2, and MSH6. Semi-quantitative scoring of immunoreactivity was based on percentage of tumor staining and staining intensity. Statistical analysis and survival were assessed using the Kaplan-Meier method and Cox regression.
  
  
  RESULTS
  Tumors were considered microsatellite unstable (MSI) when at least 2/3 markers tested negative on IHC. Overall, there was no statistically significant difference in survival between patients with MSI tumors and those with microsatellite stable tumors (MSS) (p value=0.70). However, MSI tumors which tested negative for all three markers had markedly poor survival (median survival 3 months vs 71 months, p=0.04) when compared to MSS tumors. The risk of death was 13.2 times greater among women with MSI tumors (with 3 negative markers) compared to women with MSS tumors (OR=13.20 95% CI 3.50-49.76).
  
  
  CONCLUSIONS
  Although this study has its limitation due to the small sample size, it raises the question of the prognostic significance of MSI in high grade endometrial carcinoma. It also points to the importance of evaluating three mismatch repair genes (MLH1, MSH2, and MSH6) as a prognostic indicator.
authors.affiliation: Department of Pathology, Wayne State University, Detroit, MI 48201, USA.
authors.forename: Haitham
authors.initials: H
authors.lastname: Arabi
authors.forename: Hui
authors.initials: H
authors.lastname: Guan
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Kumar
authors.forename: Michele
authors.initials: M
authors.lastname: Cote
authors.forename: Sudeshna
authors.initials: S
authors.lastname: Bandyopadhyay
authors.forename: Christopher
authors.initials: C
authors.lastname: Bryant
authors.forename: Jay
authors.initials: J
authors.lastname: Shah
authors.forename: Fadi W
authors.initials: FW
authors.lastname: Abdul-Karim
authors.forename: Adnan R
authors.initials: AR
authors.lastname: Munkarah
authors.forename: Rouba
authors.initials: R
authors.lastname: Ali-Fehmi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053842:Microsatellite Instability; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000096:biosynthesis / Q000235:genetics; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D016612:Paraffin Embedding; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein