HER2 evaluation in uterine serous carcinoma: diagnostic agreement between biopsy and resection samples

Uterine serous carcinoma (USC) is an aggressive subtype of endometrial cancer with high recurrence and mortality rates. HER2 overexpression and amplification represent important prognostic and predictive biomarkers in USC, supporting the use of HER2-targeted therapy. However, intratumoral heterogeneity and discrepancies between biopsy and hysterectomy specimens complicate accurate HER2 assessment. This study aimed to evaluate the diagnostic concordance of HER2 status between endometrial biopsy and resection samples using immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH). This retrospective study included 40 patients diagnosed with USC (2010–2020). HER2, ER, PR, and Ki-67 were evaluated by IHC, and HER2 amplification was determined by CISH in all cases. Concordance between biopsy and resection specimens was assessed using Cohen’s kappa coefficient, with resection CISH considered the gold standard. Associations between HER2 status and clinicopathologic variables were analyzed using chi-square and Mann–Whitney U tests. HER2 gene amplification was identified in 20% of cases (8/40). Biopsy CISH correctly detected 7 of 8 amplified tumors, yielding a positive predictive value (PPV) of 100% and a negative predictive value (NPV) of 97%. Only one true discordant case was observed. Concordance between biopsy and resection HER2 status was excellent (κ = 0.918). HER2-positive tumors demonstrated significantly higher Ki-67 proliferation indices (median 77% vs. 67%, p < 0.001) and were more frequently associated with advanced FIGO stage (p = 0.045). No significant associations were found between HER2 status and ER, PR, or LVI. Biopsy-based HER2 testing shows excellent concordance with resection specimens and reliably predicts HER2 amplification in USC. The findings highlight the utility of preoperative biopsies for HER2 assessment and affirm the importance of CISH confirmation in borderline (1 + and 2+) IHC categories. Standardized HER2 testing criteria specific to USC remain essential to optimize patient selection for targeted therapy.