Investigation of HER2 expression in primary and metastatic tubo-ovarian high-grade serous carcinomas

This study included 77 cases diagnosed with tubo-ovarian high-grade serous carcinoma (HGSC) between 2014 and 2023, all of which underwent cytoreductive surgery with available follow-up data. HER2 expression was assessed in primary and peritoneal metastatic sites using immunohistochemistry (IHC) and scored according to current gynecological tumor biomarker guidelines. Tumors with an IHC score of 2+ were further evaluated using HER2/CEP17 dual FISH analysis. The frequency of HER2 positivity and its relationship with clinicopathological features such as stage, bilaterality, lymphovascular invasion (LVI), p53 expression status, overall survival, lymph node involvement, and distant metastasis were examined. In the 77 cases analyzed, HER2 scores were as follows: 0 (53.2%, 41 patients), 1+ (35.1%, 27 patients), 2+ (9.1%, 7 patients), and 3+ (2.6%, 2 patients). HER2 expression patterns were consistent between primary and metastatic peritoneal sites. Among the 7 patients with a 2+ score, FISH analysis confirmed HER2 overexpression/amplification in 2 cases. A total of 4 cases (5.2%) exhibited HER2 overexpression and amplification. No statistically significant correlation was found between HER2 positivity and factors such as menopausal status, ovarian surface involvement, bilaterality, tubal lesions, p53 expression pattern, distant metastasis, lymph node metastasis, LVI, FIGO stage, progression, or overall survival (p>0.05). HER2 was concluded to play a limited role as a prognostic or predictive biomarker and did not correlate with clinicopathological features. Although HER2 positivity was higher in tumors with aggressive features, the lack of statistical significance in our results is likely due to the limited sample size. Consequently, HER2 positivity is considered a rare molecular feature in tubo-ovarian HGSC, consistent with the literature. While anti-HER2 therapies may be considered in selected cases, further studies with larger cohorts are necessary.