Faculty Collaboration Database

Microsatellite instability and epigenetic inactivation of MLH1 and outcome of patients with endometrial carcinomas of the endometrioid type. J Clin Oncol 2007 May 20;25(15):2042-8

Date

05/22/2007

Pubmed ID

17513808

DOI

10.1200/JCO.2006.08.2107

Scopus ID

2-s2.0-34249949422 (requires institutional sign-in at Scopus site)   173 Citations

Abstract

PURPOSE: Most studies of microsatellite instability (MSI) and outcomes in endometrial cancer patients have included varied histologic subtypes. Nonetheless, MSI occurs almost exclusively in endometrioid tumors. The impact of MSI on outcomes in patients with endometrial cancer is controversial. We sought to determine whether MSI and MLH1 methylation are associated with clinicopathologic variables and survival outcomes in a large series of patients with endometrial carcinomas of the endometrioid type.

PATIENTS AND METHODS: Tumor samples, blood, and clinicopathologic data were prospectively collected and analyzed for 446 patients with endometrioid carcinomas. MSI was determined using five National Cancer Institute (NCI) consensus panel markers, and the methylation status of the MLH1 promoter was determined by combined bisulfite restriction analysis (COBRA). Associations with clinicopathologic variables and survival outcomes were evaluated.

RESULTS: MSI was identified in 147 cases (33%). MSI was associated with higher International Federation of Gynecology and Obstetrics (FIGO) grade (P < .0001). MSI+ tumors without MLH1 methylation were associated with younger age (P < .001). MSI was not associated with overall survival (OS; hazard ratio [HR], 1.011; 95% CI, 0.688 to 1.484; P = .96) or disease-free survival (DFS; HR 0.951; 95% CI, 0.554 to 1.635; P = .86). The combined MSI/MLH1 methylation status (treating MSI- as the reference) did not predict OS (MSI+/MLH1-U: HR, 0.62; 95% CI, 0.27 to 1.44; P = .26; MSI+/MLH1-M: HR, 0.95; 95% CI, 0.62 to 1.46; P = .82) or DFS (MSI+/MLH1-U: HR, 0.51; 95% CI, 0.22 to 1.19; P = .12; MSI+/MLH1-M: HR, 0.93; 95% CI, 0.62 to 1.40; P = .72).

CONCLUSION: MSI is not associated with survival in patients with endometrioid endometrial cancer.

Author List

Zighelboim I, Goodfellow PJ, Gao F, Gibb RK, Powell MA, Rader JS, Mutch DG

Author

Janet Sue Rader MD Chair, Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adaptor Proteins, Signal Transducing
Carcinoma, Endometrioid
Cohort Studies
DNA Methylation
DNA Repair
Endometrial Neoplasms
Epigenesis, Genetic
Female
Humans
Microsatellite Instability
Microsatellite Repeats
Middle Aged
MutL Protein Homolog 1
MutS Homolog 2 Protein
Nuclear Proteins
Polymerase Chain Reaction
Prospective Studies