RT Journal Article SR Electronic T1 Identification of TP53 mutated group using a molecular and immunohistochemical classification of endometrial carcinoma to improve prognostic evaluation for adjuvant treatments JF International Journal of Gynecologic Cancer JO Int J Gynecol Cancer FD BMJ Publishing Group Ltd SP 640 OP 647 DO 10.1136/ijgc-2019-000871 VO 30 IS 5 A1 Guillaume Beinse A1 Bastien Rance A1 Pierre-Alexandre Just A1 Brigitte Izac A1 Franck Letourneur A1 Nathaniel Edward Bennett Saidu A1 Sandrine Chouzenoux A1 Carole Nicco A1 François Goldwasser A1 Frederic Batteux A1 Catherine Durdux A1 Charles Chapron A1 Eric Pasmant A1 Karen Leroy A1 Jerome Alexandre A1 Bruno Borghese YR 2020 UL http://ijgc.bmj.com/content/30/5/640.abstract AB Introduction Molecular classification of endometrial carcinoma has been proposed to predict survival. However, its role in patient management remains to be determined. We aimed to identify whether a molecular and immunohistochemical classification of endometrial carcinoma could improve decision-making for adjuvant therapy.Methods All consecutive patients treated for endometrial carcinoma between 2010 and 2017 at Cochin University Hospital were included. Clinical risk of relapse was based on European Society for Medical Oncology-European Society of Gynaecological Oncology-European SocieTy for Radiotherapy & Oncology (ESMO-ESGO-ESTRO) consensus. The clinical event of interest was event-free survival. Formalin-fixed paraffin-embedded tissue samples were processed for histopathological analysis and DNA extraction. The nuclear expression of mismatch repair and TP53 proteins was analyzed by immunohistochemistry. Next-generation sequencing of a panel of 15 genes including TP53 and POLE was performed using Ampliseq panels on Ion Torrent PGM (ThermoFisher). Tumors were allocated into four molecular groups using a sequential method based on next-generation sequencing and immunohistochemistry data: (1) POLE/ultramutated-like; (2) MSI/hypermutated-like (mismatch repair-deficient); (3) TP53-mutated (without POLE mutations or mismatch repair deficiency); (4) not otherwise specified (the remaining tumors).Results 159 patients were included; 125 tumors were available for molecular characterization and distributed as follows: (1) POLE/ultramutated-like: n=4 (3%); (2) MSI/hypermutated-like: n=35 (30%); (3) TP53-mutated: n=30 (25%); and (4) not otherwise specified: n=49 (42%). Assessing the TP53 status by immunohistochemistry only rather than next-generation sequencing would have misclassified 6 tumors (5%). TP53-mutated tumors were associated with poor prognosis, independently of International Federation of Gynecology and Obstetrics (FIGO) stage and histological grade (Cox-based adjusted hazard ratio (aHR) 5.54, 95% CI 2.30 to 13.4), and independently of clinical risk of relapse (aHR 3.92, 95% CI 1.59 to 9.64). Among patients with FIGO stage I–II tumors, 6 (38%) TP53-mutated tumors had low/intermediate clinical risk of relapse and did not receive adjuvant chemotherapy or radiotherapy.Conclusion Endometrial carcinoma molecular classification identified potentially under-treated patients with poor molecular prognosis despite being at low/intermediate clinical risk of relapse. Consideration of molecular classification in adjuvant therapeutic decisions should be evaluated in prospective trials.