TY - JOUR
T1 - The Prognostic Effect of Immune Cell Infiltration Depends on Molecular Subtype in Endometrioid Ovarian Carcinomas
AU - Heinze, Karolin
AU - Cairns, Evan S.
AU - Thornton, Shelby
AU - Harris, Bronwyn
AU - Milne, Katy
AU - Grube, Marcel
AU - Meyer, Charlotte
AU - Karnezis, Anthony N.
AU - Fereday, Sian
AU - Garsed, Dale W.
AU - Leung, Samuel C.Y.
AU - Chiu, Derek S.
AU - Moubarak, Malak
AU - Harter, Philipp
AU - Heitz, Florian
AU - McAlpine, Jessica N.
AU - DeFazio, Anna
AU - Bowtell, David D.L.
AU - Goode, Ellen L.
AU - Pike, Malcolm
AU - Ramus, Susan J.
AU - Pearce, C. Leigh
AU - Staebler, Annette
AU - K€obel, Martin
AU - Kommoss, Stefan
AU - Talhouk, Aline
AU - Nelson, Brad H.
AU - Anglesio, Michael S.
N1 - Publisher Copyright:
© 2023 The Authors.
PY - 2023/9/1
Y1 - 2023/9/1
N2 - 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 tumorinitiating 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 (TILBminus) 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.
AB - 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 tumorinitiating 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 (TILBminus) 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.
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U2 - 10.1158/1078-0432.CCR-22-3815
DO - 10.1158/1078-0432.CCR-22-3815
M3 - Article
C2 - 37339172
AN - SCOPUS:85169503399
SN - 1078-0432
VL - 29
SP - 3471
EP - 3483
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 17
ER -