Impact of microsatellite instability (MSI) on survival in high grade endometrial carcinoma

• Published in: Gynecologic oncology Vol. 113; no. 2; pp. 153 - 158
• Main Authors: Arabi, Haitham, Guan, Hui, Kumar, Sanjeev, Cote, Michele, Bandyopadhyay, Sudeshna, Bryant, Christopher, Shah, Jay, Abdul-Karim, Fadi W, Munkarah, Adnan R, Ali-Fehmi, Rouba
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-05-2009
• Subjects: Adaptor Proteins, Signal Transducing - biosynthesis; Adaptor Proteins, Signal Transducing - genetics; Adult; Aged; Aged, 80 and over; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - genetics; Endometrial carcinoma; Endometrial Neoplasms - genetics; Endometrial Neoplasms - metabolism; Endometrial Neoplasms - pathology; Endometrial Neoplasms - surgery; Female; Hematology, Oncology and Palliative Medicine; High grade; Humans; Immunohistochemistry; Microsatellite Instability; Middle Aged; MSI; MutL Protein Homolog 1; MutS Homolog 2 Protein - biosynthesis; MutS Homolog 2 Protein - genetics; Nuclear Proteins - biosynthesis; Nuclear Proteins - genetics; Obstetrics and Gynecology; Paraffin Embedding; Prognosis; Retrospective Studies; Survival Rate; Type-I and II Endometrial carcinoma; Type-I and II Endometrial carcinoma; MSI; Microsatellite instability; Endometrial carcinoma; High grade
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2009.02.004

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. Result 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). Conclusion 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.