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[858] Impact of Microsatellite Instability (MSI) on Survival in High Grade Endometrial Carcinoma
MH Arabi, M Cote, CS Bryant, JP Shah, AR Munkarah, R Ali-Fehmi. Wayne State University, Detroit, MI
Background: MSI is a hallmark of defective DNA- mismatch repair during replication. Genetic instability resulting from the inactivation of mismatch repair system genes (MLH1, MSH2, and MSH6) is known to be one of the molecular pathways involved in oncogenesis. The objective of this study was to identify by immunohistochemically (IHC), the correlation between MSI and survival in high grade (HG), Type I (T1) and Type II (T2) endometrial carcinomas (EC).
Design: Between 1995 and 2002, we identified 460 patients with EC who underwent hysterectomy. 91 HG EC cases (T1=44 and T2=47) were available. Two paraffin blocks from each case were immunostained using antibodies against MLH1, MSH2, and MSH6. Semi-quantitative scoring of immunoreactivity was based on percentage of tumor staining and staining intensity. The distribution of demographic variables and tumor characteristics were available using SEER and institutional databases. Statistical analysis and survival data were calculated using the Kaplan-Meier method 
Cox regression.
Results: The mean age was 60.7 and 62.6 years for T1 and T2 EC, respectively. The study population included 44 white and 47 black patients. The overall distribution by stage was 34 Stage I and 57 Stage II/III/IV. 58 patients (T1=31, T2=27) were alive at the time of the study. 33 (T1=13, T2=20) were deceased from cancer-related causes. The median survival was 45.5 months for T1 and 27.0 months for T2. IHC status is described in table 1.
| MSI Status | Type I | Type II |
|---|---|---|
| 0 markers positive | 4 (9.1%) | 1 (2.1%) |
| 1 marker positive | 10 (22.7%) | 10 (21.3%) |
| 2 markers positive | 9 (20.5%) | 12 (25.5%) |
| 3 markers positive | 21 (47.7%) | 24 (51.1%) |
Tumors were considered microsatellite unstable when immunostaining was negative for all three markers. MSI was present in 5 cases (T1=4, T2=1). After adjusting for race, stage and tumor type, the risk of death was 13.2 times greater among women with MSI tumors compared to women with non-MSI tumors (OR=13.20 95% CI 3.50-49.76). A significant difference in survival was noted for MSI tumors (3.3 months) compared to non-MSI tumors (71.6 months) in this cohort of patients (p=0.004).
Conclusions: Although this study has its limitation due to the small sample size, it confirms the prognostic significant of MSI in high grade endometrial carcinoma, the risk of death was significantly higher in patients whose tumors tested negative for the three mismatch repair genes MLH1, MSH2, and MSH6. Evaluating these genes might be valuable prognostic indicator for survival in HG EC patients.
Category: Gynecologic
Monday, March 26, 2007 8:30 AM
Platform Session: Section C, Monday Morning