Journal Article

Lynch syndrome-related non-endometrioid endometrial cancer: analysis of outcomes

Liberale, Viola, Paolini, Biagio, Chiappa, Valentina, Carnevali, Ileana, Ricci, Maria Teresa, Tibiletti, Maria Grazia, Ditto, Antonino, Raspagliesi, Francesco, Vitellaro, Marco, Murgia, Ferdinando, Bogani, Giorgio, Milione, Massimo, Ghezzi, Fabio

2020

Overview

ObjectiveWomen with Lynch syndrome have a risk up to 40–60% of developing endometrial cancer, which is higher than their risk of developing colorectal or ovarian cancer. To date, no data on the outcomes of patients with Lynch syndrome diagnosed with non-endometrioid endometrial cancer are available. The goal of this study was to evaluate the outcome of patients with Lynch syndrome diagnosed with non-endometrioid endometrial cancer.MethodsData from consecutive patients diagnosed with Lynch syndrome and with a histological diagnosis of non-endometrioid endometrial cancer were retrospectively collected in two referral institutes in Italy. A case–control comparison (applying a propensity matching algorithm) was performed in order to compare patients with proven Lynch syndrome and controls. Inclusion criteria were: (a) histologically-proven endometrial cancer; (b) detection of a germline pathogenic variant in one of the MMR genes; (c) adequate follow-up. Only carriers of pathogenic or likely pathogenic variants (ie, class 5 and 4 according to the InSiGHT classification) were included in the study. Survival outcomes were assessed using KaplanMeier and Cox models.ResultsOverall, 137 patients with Lynch syndrome were collected. Mean patient age was 49.2 (10.9) years. Genes involved in the Lynch syndrome included MLH1, MSH2, and MSH6 in 43%, 39%, and 18% of cases, respectively. The study population included 27 patients with non-endometrioid endometrial cancer, who were matched 1:2 with patients with sporadic cancers using a propensity matching algorithm. After a median follow-up of 134 months (range 1–295), 2 (7.4%) of the 27 patients developed recurrent disease (3 and 36 months) and subsequently died of disease (7 and 91 months). Patients diagnosed with Lynch syndrome experienced better disease-free survival (HR 7.86 (95% CI 1.79 to 34.5); p=0.006) and overall survival (HR 5.33 (95% CI 1.18 to 23.9); p=0.029) than controls.ConclusionsNon-endometrioid endometrial cancer occurring in patients with Lynch syndrome might be associated with improved oncologic outcomes compared with controls. Genetic/molecular profiling should be investigated in order to better understand the mechanism underlying the prognosis.

• Publisher: Elsevier Inc,by the International Gynecologic Cancer Society and the European Society of Gynaecological Oncology,Elsevier Limited
• Subject: Adult / Aged / Cancer therapies / Carcinoma, Endometrioid - genetics / Carcinoma, Endometrioid - pathology / Carcinoma, Endometrioid - surgery / Case-Control Studies / Cohort Studies / Colorectal cancer / Colorectal Neoplasms, Hereditary Nonpolyposis - genetics / Colorectal Neoplasms, Hereditary Nonpolyposis - pathology / Colorectal Neoplasms, Hereditary Nonpolyposis - surgery / Disease-Free Survival / DNA-Binding Proteins - genetics / Endometrial cancer / endometrial neoplasms / Endometrial Neoplasms - genetics / Endometrial Neoplasms - pathology / Endometrial Neoplasms - surgery / Female / Genes / Genetic disorders / Histology / Humans / Lynch syndrome II / Medical prognosis / Middle Aged / Mutation / MutL Protein Homolog 1 - genetics / MutS Homolog 2 Protein - genetics / Ovarian cancer / Patients / Retrospective Studies / Survival Rate / Tumors / Uterine cancer / uterine neoplasms