HER2 patterns vary across ovarian cancer subtypes

A study of 219 epithelial ovarian cancers found that human epidermal growth factor receptor 2 (HER2) protein expression and gene amplification varied substantially by histologic subtype. High-grade serous carcinoma had relatively low rates of strong HER2 protein staining and amplification, while mucinous carcinoma had the highest rates. In the high-grade serous subgroup, higher HER2 immunohistochemistry scores were associated with worse progression-free survival, but not overall survival.

Researchers evaluated 184 cases of high-grade serous carcinoma, 11 endometrioid carcinomas, 11 clear cell carcinomas and 13 mucinous carcinomas. HER2 protein expression was measured by immunohistochemistry, or IHC, and HER2 gene amplification was assessed by silver in situ hybridization, or SISH. The analysis compared results across the four histologic groups and examined their relationships with clinicopathologic characteristics and survival outcomes.

Strong HER2 IHC 3+ expression occurred in 1.1% of high-grade serous carcinomas, and amplification was detected in 3.3%. Mucinous carcinoma showed the highest observed proportions of IHC 3+ expression and amplification, at 23.1% and 38.5%, respectively. Across the tumors, IHC 0–1+ results were strongly concordant with non-amplification, while IHC 3+ results were strongly concordant with amplification; both associations had p<0.001.

IHC 2+ cases were equivocal, with amplification varying according to histologic subtype. Approximately 30% of the high-grade serous carcinomas were classified as HER2-low. Among the high-grade serous carcinomas, higher HER2 IHC scores were significantly associated with worse progression-free survival, with p=0.028.

The same association was not observed for overall survival. HER2 amplification status and the broader HER2-zero, HER2-low and HER2-high grouping did not show statistically significant associations with either survival outcome. These results describe statistical associations within the study cohort and do not establish that HER2 expression caused differences in progression or survival.

The findings support evaluating HER2 according to ovarian cancer histologic subtype. They also identify a substantial HER2-low group within high-grade serous carcinoma, which the authors say may be relevant to future HER2-low–directed therapeutic strategies. The cohort was limited to 219 cancers with an uneven distribution among the four histologic subgroups, so the reported percentages describe this selected population rather than necessarily representing rates throughout ovarian cancer.

Subject of Research: HER2 expression, amplification and survival associations in epithelial ovarian cancer

Article Title: HER2 expression and HER2-low status in high-grade serous ovarian carcinoma: clinicopathologic and prognostic implications

Article References: Seok, J., Ahn, B., Kim, M., Lee, J., & Park, E. (2026). HER2 expression and HER2-low status in high-grade serous ovarian carcinoma: clinicopathologic and prognostic implications. BMC Cancer. https://doi.org/10.1186/s12885-026-16694-9

Image Credits: AI Generated

DOI: 10.1186/s12885-026-16694-9

Keywords: HER2, ovarian cancer, high-grade serous carcinoma, HER2-low, immunohistochemistry, gene amplification, progression-free survival, biomarkers, histologic subtype, expression, status, high-grade