abstract: Prospective evaluation of molecular screening for Lynch syndrome in patients with endometrial cancer ≤ 70 years.

Blogger's Note: age >50 yrs will be at issue

Gynecol Oncol. 2012 Feb 1.

Abstract

OBJECTIVE:

Lynch syndrome (LS) is a hereditary syndrome that predisposes to multiple malignancies including endometrial cancer (EC). We aimed to evaluate a diagnostic strategy for LS based on routine analysis of microsatellite instability (MSI) and immunohistochemical (IHC) staining for mismatch repair (MMR) proteins in tumor tissue of all newly diagnosed EC patients ≤70years.

METHODS:

Consecutive EC patients ≤70years were included prospectively in eight Dutch centers. EC specimens were analyzed for MSI, IHC of four MMR proteins, MMR gene methylation status and BRAF-mutations. Tumors were classified as; 1) likely to be caused by LS, 2) sporadic MSI-H, or 3) microsatellite stable (MSS).

RESULTS:

Tumor specimens of 179 patients (median age 61years, IQR 57-66) were analyzed. In our study 92% of included patients were over 50 years of age. Eleven EC patients were found likely to have LS (6%; 95% CI 3-11%), including 1 patient suspected of an MLH1, 2 of an MSH2, 6 of an MSH6 and 2 of a PMS2 gene defect. Germline mutation analyses revealed 7 MMR gene germline mutations. Ten patients likely to have LS (92%) were older than 50years. In addition, 31 sporadic MSI-H tumors with MLH1 promoter hypermethylation (17%; 95% CI 13-24%) were identified.

CONCLUSIONS:

Molecular screening for LS in patients with EC diagnosed≤70years, leads to identification of a profile likely to have LS in 6% of cases. New screening guidelines for LS are needed, including recommendations for EC patients older than 50years of age.