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Updated: Jan 10, 2026
Validated Immunochemical Assay for Comprehensive Determination of the Human Epidermal Growth Factor Receptor 2 Released from and Bound to Cells
Published on: May 9, 2025
HER2 immunoreactivity in advanced non-p53abn endometrial carcinoma: Association with clinical features, prognosis,
Yining Zhen1, Yinbo Xiao1, Yang Zhou1
1Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Background:
Human epidermal growth factor receptor 2 (HER2) is an emerging therapeutic target in endometrial carcinoma (EC). Current guidelines recommend routine HER2 testing for p53 abnormal (p53abn) tumors, potentially underestimating its value in non-p53abn cases. This study aimed to assess the incidence and clinical relevance of HER2 immunoreactivity in advanced non-p53abn EC.
Methods:
HER2 immunohistochemistry and next-generation sequencing were performed in 128 advanced EC patients. Clinicopathological features, survival, and molecular alterations were compared according to HER2 immunoreactivity.
Results:
Of all patients, 18.8 % were HER2 2 + /3 + , 28.9 % were HER2 1 + , and 52.3 % were HER2 0. Molecular classification included 1.6 % POLE mutant, 35.2 % mismatch repair-deficient/ microsatellite instability-high, 29.7 % p53abn, and 33.6 % no specific molecular profile (NSMP). In the non-p53abn group, HER2 3 + was less frequent than in the p53abn group, whereas the frequencies of HER2 2 + and 1 + did not differ significantly between the two groups. In non-p53abn patients, HER2 2 + /3 + occurred most frequently in clear cell carcinoma (CCC, 6/11, 54.5 %) and was associated with adnexal metastasis (2 +/3 + vs. 1 +, 66.7 % vs. 15.4 %, P < 0.05). No survival differences were observed among non-p53abn patients by HER2 immunoreactivity, however, within the NSMP subgroup, both overall and progression-free survival were worse in HER2 2 + /3 + compared with 1 + (log-rank P < 0.05). In non-p53abn ECs, KRAS mutations were significantly less frequent in HER2 2 + /3 + group (2 +/3 + vs. 1 +, 6.7 % vs. 46.2 %, P < 0.05).
Conclusions:
HER2 2 + /3 + immunoreactivity was detected in 16.7 % of advanced non-p53abn EC, particularly enriched in CCC. These findings highlight the potential clinical significance of HER2 testing in non-p53abn patients.
