ER, PR, and HER2 triple positivity and triple negativity are associated with adverse prognostic significance in endometrial serous carcinoma

Endometrial serous carcinoma (ESC) is an aggressive tumor of the mullerian system. The prognostic significance of the combined status of HER2, estrogen receptor (ER), and progesterone receptor (PR) on ESC's survival and clinicopathologic outcome remains inadequately reported and understood. In this study, we retrospectively analyzed sixty-one ESC cases diagnosed at our institution between January 2017 and April 2024 for overall survival outcomes and pathologic presentation. Most ESC cases were ER-positive (n = 53, 87%) and PR-positive (n = 42, 69%), while HER2 was positive in 43% of cases (n = 26). Subclassification based on the combined status of ER, PR and HER2 revealed significant heterogeneity of overall survival within both HER2-positive and negative groups. Notably, the triple-positive subgroup had the shortest median survival and poorer prognosis than the other subgroups (p = 0.04; median survival: 394 vs. 676.5 days). The triple-negative subgroup demonstrated significantly worse overall survival as well. The unfavorable clinical outcome in these subgroups was associated with a higher frequency of lower uterine segment, cervical, and lymph node involvement. This study demonstrates that combined HER2, ER, and PR status provides valuable prognostic information in ESC, enabling the identification of subgroups with distinct clinical behaviors. Stratification based on combined receptor status may facilitate more personalized treatment approaches and improve clinical outcomes in this aggressive malignancy. Further large-scale studies are needed to validate these findings and explore targeted therapeutic strategies for high-risk subgroups.