The presence of an endometrioid component does not alter the clinicopathologic profile or survival of patients with uterine serous cancer: A gynecologic oncology group (GOG/NRG) study of 934 women

Abstract

Objective: While most cases of endometrial cancer can readily be classified as pure endometrioid, pure serous, or another type, others show an apparent mixture of serous and endometrioid components, or indeterminate serous versus endometrioid features. Since serous histology carries a worse prognosis than endometrioid, Gynecologic Oncology Group protocol GOG-8032 was established to examine whether the presence of a non-serous component is a favorable feature in an otherwise serous cancer.

Methods: 934 women with serous cancer were prospectively identified among a larger group enrolled in GOG-0210. Six expert gynecologic pathologists classified each case as pure serous (SER, n=663), mixed serous and endometrioid (SER-EM-M, n=138), or indeterminate serous v. endometrioid (SER-EM-I, n=133) by H&E morphology. Follow-up data from GOG-0210 were analyzed.

Results: The subgroups did not differ on BMI, race, ethnicity, lymphovascular invasion, cervical invasion, ovary involvement, peritoneal involvement, omental involvement, FIGO stage, or planned adjuvant treatment. SER-EM-M patients were younger (p=0.0001) and less likely to have nodal involvement (p=0.0287). SER patients were less likely to have myoinvasion (p=0.0002), and more likely to have adnexal involvement (p=0.0108). On univariate analysis, age, serous subtype, race, and components of FIGO staging predicted both progression-free and overall survival. On multiple regression, however, serous subtype (SER, SER-EM-M, or SER-EM-I) did not significantly predict survival.

Conclusions: There were few clinicopathologic differences between cases classified as SER, SER-EM-M, and SER-EM-I. Cases with a mixture of serous and endometrioid morphology, as well as cases with morphology indeterminate for serous v. endometrioid type, had the same survival as pure serous cases. NCT#: NCT00340808.

Keywords: Endometrial carcinoma; Endometrioid carcinoma; Malignant mixed tumors; Pathology; Serous carcinoma; Survival analysis.

Conflict of interest statement

Declaration of Competing Interest Dr. Hagemann served as a consultant for Change Healthcare related to molecular pathology. He also provided expert witness services to multiple clients regarding gynecologic and breast cases. Dr. Powell reports personal fees from Tesaro, Merck, Roche/Genentech, Clovis Oncology, AstraZeneca, Johnson & Johnson, Eisai and Abbvie. Dr. Gunderson's institution received money for consultancy from Agenus, Cordgenics, Leap, Clovis, and GSK. Dr. Mathews reports grants from Syros, Deciphera, AstraZeneca, Astellas Pharma, Tesaro/GSK, Seattle Genetics and Regeneron outside the submitted work. Dr. Pearl received a grant from the Gynecologic Oncology Group. He also has grants/grants pending from GOG/NIH. He has received Royalties from Vivitek, Inc. via SBU Research Foundation. Dr. Alvarez Secord reports grants from AbbVie, Amgen, AstraZeneca, Clovis, Astellas Pharma Inc., Boehringer Ingelheim, Briston Meyers Squibb, Eisai, Endocyte, Exelixis, Incyte, Merck, PharmaMar, Immutep Ltd., Roche/Genentech, Seattle Genetics, Inc., Tesaro/GSK, VBL Therapeutics, National Cancer Trial Network; honoraria from Aravive, AstraZeneca, Clovis, Cordgenics, Eisai, Janssen/Johnson & Johnson, Merck, Mersana, OncoQuest, Roche/Genentech, Tesaro/GSK Advisory Boards; participation on Clinical Trial Steering Committees (uncompensated) for Roche/Genentech and VBL Therapeutics; and member of GOG-Foundation Board of Directors, outside the submitted work. Dr. Park received grant funding from NIH/NCI P30 CA008748. Dr. Soslow is on a core grant from the NIH. He has received Royalties from Springer and Cambridge University Press and payment for development of educational presentations from Ebix/Oakstone. All other co-authors have no Conflicts of Interest to declare.

Copyright © 2021 Elsevier Inc. All rights reserved.

Figures

Figure 1.

Pure serous endometrial cancer (SER), (A) 100x and (B) 400x original magnification. Mixed serous and endometrioid endometrial cancer (SER-EM-M), as determined by histologic review by the G6 pathologists. A single case shows both (C) endometrioid-like areas and (D) serous-like areas, 200x original magnification. The term “mixed” was applied when disparate cell types could be identified. Endometrial cancer with features intermediate between endometrioid and serous, so-called indeterminate cancer (SER-EM-I) as determined by the G6 pathologists. H&E examination at (E) 100x and (F) 400x shows cancer with a single morphology, with cells sharing some features of serous carcinoma (high-grade nuclei, high mitotic rate) and endometrioid carcinoma (tall columnar cells).

Figure 2.

Predicted (A) progression-free and (B) overall survival of patients with three subtypes of serous cancer for stage I vs stage III based on a Cox PH model adjusted for age (67 years), race (white), and myometrial invasion (inner half).