Impact of microsatellite instability (MSI) on survival in high grade endometrial carcinoma.
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.
Arabi
Haitham
H
Department of Pathology, Wayne State University, Detroit, MI 48201, USA.
Guan
Hui
H
Kumar
Sanjeev
S
Cote
Michele
M
Bandyopadhyay
Sudeshna
S
Bryant
Christopher
C
Shah
Jay
J
Abdul-Karim
Fadi W
FW
Munkarah
Adnan R
AR
Ali-Fehmi
Rouba
R
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
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