Endometrial cancer following endometrial intraepithelial neoplasia versus biopsy-diagnosed cancer: clinicopathological and immunohistochemical features.

OBJECTIVE: To compare clinicopathological characteristics and immunohistochemistry-based molecular profiles between endometrial cancers diagnosed after preoperative endometrial interepithelial neoplasia (EIN) and cancers diagnosed preoperatively by biopsy. STUDY DESIGN: This retrospective cohort study included women treated for endometrial cancer at a tertiary referral center from January 2010 through January 2026. The primary comparison included an EIN group, in which carcinoma was diagnosed in the hysterectomy specimen after EIN, and a group with carcinoma confirmed by preoperative biopsy. Clinicopathological data were abstracted from medical records. Molecular assessment used mismatch repair and p53 immunohistochemistry; POLE sequencing was unavailable. RESULTS: Of 173 patients, 38 comprised the EIN group, 133 had biopsy-diagnosed carcinoma, and two without preoperative biopsy were excluded from the primary comparison. The EIN group had fewer high-grade tumors (4/38 [10.5%] vs 58/133 [43.6%]; p < 0.001), less deep myometrial invasion (13/38 [34.2%] vs 85/132 [64.4%]; p = 0.001), and an earlier stage distribution (p = 0.009). Among patients with complete IHC profiles, NSMP-like, MMR-deficient, and p53-abnormal profiles occurred in 20/33 (60.6%), 7/33 (21.2%), and 6/33 (18.2%) versus 63/133 (47.4%), 28/133 (21.1%), and 42/133 (31.6%), respectively (overall exact p = 0.264). CONCLUSIONS: Endometrial cancers diagnosed after EIN were significantly lower-grade, less invasive, and earlier-stage than biopsy-diagnosed cancers, with no statistically significant difference in the assessed MMR/p53 IHC profiles. These findings support systematic postoperative pathological and molecular risk assessment when carcinoma is identified after EIN.