Reid BM, Vyas S, Chen Z, et al. - In this study, the prognostic value of enhancer of zesta homologue 2 (EZH2), an essential component of polycomb repressive complex 2 (PRC2) that contributes to tumor progression and chemo-resistance, has been comprehensively examined across the morphologic and molecular spectra of high-grade serous ovarian carcinoma (HGSOC) by using both immunohistochemistry (IHC) and proteogenomic technologies. Researchers performed IHC of EZH2 utilizing a tissue microarray of 79 HGSOC scored (+/−) for lymphovascular invasion (LVI), tumor-infiltrating lymphocytic aggregates ≥ 1 mm (TIL) and architectural growth patterns. Variation in EZH2 expression was noted based on its interactions with immunologic pathways and tumor microenvironment, influencing the prognostic interpretation. They identified EZH2 expression as predictive of chemotherapy resistance and shorter survival; however, this was noted only for HGSOC with distinct morphologic features, including those without infiltrating lymphocytes (TIL-) and those with lymphovascular invasion (LVI+). Although EZH2 overexpression correlates with biologically aggressive epithelial ovarian cancer (EOC) features, the prognostic associations have been independent of these factors. This analysis overall indicated a mixed prognostic ability for EZH2 dependent on immunogenic and angiogenic tumor properties.