The Prognostic Effect of Immune Cell Infiltration Depends on Molecular Subtype in Endometrioid Ovarian Carcinomas

Heinze, K; Cairns, ES; Thornton, S; Harris, B; Milne, K; Grube, M; Meyer, C; Karnezis, AN; Fereday, S; Garsed, DW; Leung, SCY; Chiu, DS; Moubarak, M; Harter, P; Heitz, F; McAlpine, JN; DeFazio, A; Bowtell, DDL; Goode, EL; Pike, M; Ramus, SJ; Pearce, CL; Staebler, A; Kobel, M; Kommoss, S; Talhouk, A; Nelson, BH; Anglesio, MS

Author(s): Heinze, K; Cairns, ES; Thornton, S; Harris, B; Milne, K; Grube, M; Meyer, C; Karnezis, AN; Fereday, S; Garsed, DW; Leung, SCY; Chiu, DS; Moubarak, M; Harter, P; Heitz, F; McAlpine, JN; DeFazio, A; Bowtell, DDL; Goode, EL; Pike, M; Ramus, SJ; Pearce, CL; Staebler, A; Kobel, M; Kommoss, S; Talhouk, A; Nelson, BH; Anglesio, MS;
Details: Publication Year 2023-09-01,Volume 29,Issue #17,Page 3471-3483
Journal Title: Clinical Cancer Research
Publication Type: Research article
Abstract: PURPOSE: Endometrioid ovarian carcinoma (ENOC) is the second most-common type of ovarian carcinoma, comprising 10%-20% of cases. Recently, the study of ENOC has benefitted from comparisons to endometrial carcinomas including defining ENOC with four prognostic molecular subtypes. Each subtype suggests differential mechanisms of progression, although tumor-initiating events remain elusive. There is evidence that the ovarian microenvironment may be critical to early lesion establishment and progression. However, while immune infiltrates have been well studied in high-grade serous ovarian carcinoma, studies in ENOC are limited. EXPERIMENTAL DESIGN: We report on 210 ENOC, with clinical follow-up and molecular subtype annotation. Using multiplex IHC and immunofluorescence, we examine the prevalence of T-cell lineage, B-cell lineage, macrophages, and populations with programmed cell death protein 1 or programmed death-ligand 1 across subtypes of ENOC. RESULTS: Immune cell infiltrates in tumor epithelium and stroma showed higher densities in ENOC subtypes with known high mutation burden (POLEmut and MMRd). While molecular subtypes were prognostically significant, immune infiltrates were not (overall survival P > 0.2). Analysis by molecular subtype revealed that immune cell density was prognostically significant in only the no specific molecular profile (NSMP) subtype, where immune infiltrates lacking B cells (TILB minus) had inferior outcome (disease-specific survival: HR, 4.0; 95% confidence interval, 1.1-14.7; P < 0.05). Similar to endometrial carcinomas, molecular subtype stratification was generally superior to immune response in predicting outcomes. CONCLUSIONS: Subtype stratification is critical for better understanding of ENOC, in particular the distribution and prognostic significance of immune cell infiltrates. The role of B cells in the immune response within NSMP tumors warrants further study.
Publisher: American Association for Cancer Research
Keywords: Female; Humans; Prognosis; Biomarkers, Tumor/genetics; *Carcinoma, Endometrioid/pathology; *Ovarian Neoplasms/pathology; *Endometrial Neoplasms/genetics/pathology; Carcinoma, Ovarian Epithelial; Tumor Microenvironment
Department(s): Laboratory Research
PubMed ID: 37339172
Publisher's Version: https://doi.org/10.1158/1078-0432.CCR-22-3815
Open Access at Publisher's Site: https://doi.org/10.1158/1078-0432.Ccr-22-3815
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-11-15 06:57:59

Last Modified: 2023-11-15 06:58:09