Epidemiological analysis of hereditary endometrial cancer in a large study population

To determine the prevalence of hereditary endometrial cancer and the clinical and molecular characteristics of hereditary endometrial cancer patients.

Standardized oncological family histories were collected from 704 consecutive patients with endometrial cancer from January 2006 to April 2012 and analyzed using internationally approved and modified diagnostic criteria based on the Amsterdam I and II criteria. Blood samples were collected from 648 patients. Paraffin embedded tissues for immunohistochemical examination were gathered from 109 patients. All patients were split into two main groups corresponding to hereditary and sporadic endometrial cancer.

The prevalence of hereditary endometrial cancer was established as 2.7 % (95 % CI 1.7-4.2 %) or 19/704 patients. 15/19 (78.9 %; 95 % CI 56.7-91.5 %) patients were diagnosed in stage I. Grade 2 tumors were the most common ones with 11/19 (57.9 %; 95 % CI 36.3-76.9 %) patients. In the MLH1 gene, two patients were carrying the missense mutations P640S (rs63749792) and I219V (rs1799977) each. In the MSH2 gene, one had the splice site mutation IV5+3A>T while another had the missense mutation G322D (rs4987188). In the MSH6 gene, two were carrying the frameshift mutations 2150TCAG (rs63750159) and 1050delC each. No clinically putative significant mutations were found in two patients.

No significant survival, stage and grade of differentiation differences were observed between the hereditary group and the sporadic group. Clinical and molecular investigations promote an earlier diagnosis of endometrial cancer in families where at least three first-degree relatives have endometrial cancer.