Histopathological characterization of ProMisE molecular groups of endometrial cancer

Background: After the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) development, endometrial cancer (EC) may be reclassified in four novel prognostic groups: POLE-mutated (POLE-mt), mismatch-repair-deficient (MMR-d), p53-abnormal (p53abn), p53-wild-type (p53wt). However, histopathological characteristics of each ProMisE group are still undefined. Such characterization may be useful to understand how this novel molecular classifier may change the current patient management, reducing over- and undertreatment. Aim: To provide a histopathological characterization of ProMisE groups of EC, in terms of histological grade (G3 vs G1–2), histotype, lymphovascular space invasion (LVSI), deep myometrial invasion (>50%), lymph node involvement, and European Society for Medical Oncology (ESMO) risk category. Materials and methods: A systematic review and meta-analysis was performed by searching seven electronic databases from their inception to May 2019, for studies that reported histopathological characteristics of each ProMisE group. Pooled prevalence of each histopathological characteristic of EC in each ProMisE group was calculated. Results: Four studies with 1171 patients were included in the systematic review, out of which three studies with 912 patients were included in the meta-analysis. Pooled prevalence estimates were: - in the MMR-d group, G3 = 47.4%, G1–2 = 52.6%; endometrioid = 85.8%, non-endometrioid = 14.2%; LVSI-present = 41.3%, −absent = 58.7%; deep myometrial invasion-present = 44.5%, −absent = 55.5%; lymph node involvement-present = 9.9%, −absent = 90.1%; low-risk = 30.1%, intermediate risk = 19.9%, high-risk = 50%; - in the POLE-mt group, G3 = 39.6%, G1–2 = 60.4%; endometrioid = 86.1%, non-endometrioid = 13.9%; LVSI-present = 32.7%, −absent = 67.3%; deep myometrial invasion-present = 27.3%, −absent = 72.7%; lymph node involvement-present = 0%, −absent = 100%; low-risk = 44.1%, intermediate-risk = 22.5%, high-risk = 33.4%; - in the p53-wt group, G3 = 15.6%, G1–2 = 84.4%; endometrioid = 96.7%, non-endometrioid = 3.3%; LVSI-present = 13.8%, −absent = 86.2%; deep myometrial invasion-present = 27.4%, −absent = 72.6%; lymph node involvement-present = 4.3%, −absent = 95.7%; low-risk = 59.5%, intermediate-risk = 17.3%, high-risk = 23.2%; - in the p53-abn group, G3 = 90%, G1–2 = 10%; endometrioid = 27%, non-endometrioid = 73%; LVSI-present = 48.8%, −absent = 51.2%; deep myometrial invasion-present = 48.9%, −absent = 51.1%; lymph node involvement-present = 23.7%, −absent = 76.3%; low-risk = 7.2%, intermediate-risk = 8.1%, high-risk = 84.7%. Conclusions: The histopathological characterization of the ProMisE groups suggests that many patients are currently undertreated or overtreated (especially in the POLE-mt and MMR-d groups).