The relationship between lymph node metastasis and immunohistochemical molecular subtypes in endometrial cancer: A cohort study of 339 patients

Abstract Aim This study evaluated the association between immunohistochemically (IHC) molecular subtypes and lymph node metastasis (LNM) in endometrial cancer. Methods The study included 339 patients diagnosed with endometrial cancer (EC) confined to the uterus and treated with pelvic ± para‐aortic lymph node dissection (LND), who were included in the study. Patients were divided into two groups: LNM‐negative (Group 1, n = 289) and LNM‐positive (Group 2, n = 50). All patients underwent IHC‐based molecular subtype analysis. Demographic, clinical, and histopathological characteristics were evaluated. Results The median age was 62 years (34–79) in Group 1 and 64 years (48–79) in Group 2 ( p = 0.022). Body mass index (BMI) and parity were similar between the groups ( p > 0.05). LNM was detected in 14.7% of patients (50/339). Among Group 1, 64.4% (186/289) had a non‐specific molecular profile (NSMP), 20.1% (58/289) had mismatch repair deficiency (MMRd), and 15.5% (45/289) had the p53 abnormal (p53abn) subtype. In contrast, in Group 2, 44% (22/50) were NSMP, 24% (12/50) were MMRd, and 32% (16/50) were p53abn ( p = 0.008). A statistically significant association was observed between LNM and the p53abn subtype. LNM was present in 26% (16/61) of patients with the p53abn subtype, compared to 17% (12/70) in the MMRd group and 11% (22/208) in the NSMP group. Conclusion While our study identified an association between the p53abn subtype and lymph node metastasis, this finding alone does not support using p53 status in isolation to determine lymphatic staging; instead, it should be considered a complementary marker alongside established clinicopathologic factors.