Résumé
IntroductiontHormone therapy is an effective treatment of metastatic endometrial cancer, with low toxicity and low cost. The response rate is interesting, up to 56% of clinical benefit rate is some studies. (Pautier et al., 2016) However, there is still no predictive factor of response well identified. The progesterone receptor is the only factor found, and could be proposed (grade C recommendation) before the introduction of the hormone therapy (ESMO-ESGO-ESTRO Consensus 2015).The objective of the study was to found new predictive factors of response to hormone therapy in metastatic endometrial cancer by conducting an unsupervised analysis.Material and MethodstWe conducted a retrospective review of all cases of endometrial cases in two French cancer centers between January 2000 and January 2016. Inclusion criteria were: metastatic endometrial cancer, treated by hormone therapy, histologic type endometriou00efd or serous, and FFPE sample (formalin-fixed paraffin-embedded) available. Exclusion criteria were hormone therapy received for an associated breast cancer and response not evaluable. The main endpoint (EP1) was clinical benefit defined as partial or complete response of stability longer than 6 months. Secondary endpoints were response longer than 18 months (EP2) and overall survival (OS).We performed a second histologic assessment by local experts, immunohistochemistry for estrogen (ER) and progesterone receptors (PR) and microsatellite instability-MSI- (hMLH1, hMSH2, hMSH6, PMS2).We extracted DNA from FFPE tissue to perform molecular testing. We realized analysis by Next-Generation Sequencing (NGS) with a commercial panel testing 495 genes and CGH analysis (Comparative Genome Hybridation).This study was approved by local ethic committee.ResultsOn 1052 screened endometrial cancer cases, 46 completed inclusion criteria and 38 were included. DNA extraction was not possible for 3 cases, DNA quantity was not sufficient for 3 cases and NGS was not interpretable for 2 cases. Population characteristics were: 33 cases of endomu00e9triou00efd carcinoma, 6 tumors MSI, 30 tumors with at least one positive hormonal receptor. 3 women presented a thromboembolic event, whose one severe event inducting interruption of treatment.In multivariate analysis, the only factor associated with EP1 was PTEN mutation (OR=5.92, p=0.047).Percentage of progesterone receptor expression was associated with EP2. No MSI tumors presented a long time response.Prognostic factors of OS were: age (OR=1.06, p=0.045) and at least one positive hormonal receptor (OR=0.26, p=0.031). PTEN did not reach significance (OR=0.32, p=0.077).For EP1, the association PR+ - PTEN mutated was characterized by: sensibility of 0.47, specificity of 0.94, positive predictive value (PPV) of 0.89 and negative predictive value of 0.62.For EP2, the association PR+ - PTEN mutated u2013 MSI was characterized by: sensibility of 0.67, specificity of 0.96, PPV of 0.8, NPV of 0.93.ConclusionTesting PR, PTEN and MSI status could be an effective option to select good candidates to hormone therapy in metastatic endometrial carcinoma.