Abstract

<div>AbstractPurpose:<p>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.</p>Experimental Design:<p>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.</p>Results:<p>Immune cell infiltrates in tumor epithelium and stroma showed higher densities in ENOC subtypes with known high mutation burden (<i>POLE</i>mut and MMRd). While molecular subtypes were prognostically significant, immune infiltrates were not (overall survival <i>P</i> > 0.2). Analysis by molecular subtype revealed that immune cell density was prognostically significant in only the <i>no specific molecular profile</i> (NSMP) subtype, where immune infiltrates lacking B cells (TIL<sub>B minus</sub>) had inferior outcome (disease-specific survival: HR, 4.0; 95% confidence interval, 1.1–14.7; <i>P</i> < 0.05). Similar to endometrial carcinomas, molecular subtype stratification was generally superior to immune response in predicting outcomes.</p>Conclusions:<p>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.</p></div>

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