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Human epidermal growth factor receptor 3 expression in patients with epithelial ovarian cancer: a potential target
Sho Sato1, Daisuke Shintani1, Yuki Kaneda2
1Department of Gynecologic Oncology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, Saitama, 350-1298, Japan.
Background:
Human epidermal growth factor receptor 3 (HER3), a tyrosine kinase belonging to the HER family, is a known target for cancer therapy; recently, an anti-HER3 antibody-drug conjugate (ADC) is developing. To understand HER3 expression in epithelial ovarian cancer (EOC), this study was conducted.
Methods:
We investigated the expression of HER3 in 202 patients with EOC using immunohistochemistry (IHC), and the association between HER3 expression, clinicopathological features, prognosis, and treatment timing.
Results:
Of all the cases, 55.4% had a HER3 IHC score ≥ 1 + . In particular, 78.0% of the patients with clear cell carcinoma (CCC) and 87.9% of the patients with mucinous carcinoma (MC) had a HER3 IHC score ≥ 1 + . Regarding clinicopathological features, early disease stage, feasibility of primary debulking surgery, no residual tumor, and low CA125 levels were more frequently observed in patients with a HER3 IHC score ≥ 1 + . Furthermore, a HER3 no-expression showed a significant association with a relatively short progression-free survival (PFS). And, for patients with mucinous carcinoma, those with a HER3 IHC score ≥ 1 + had poorer PFS and overall survival than those with a HER3 no-expression (no statistically significant difference). In addition, we analyzed HER3 expression at primary tumor and recurrence tumor in same patients. Thus, we observed the HER3 IHC score tended to change from 0 to ≥ 1 + in recurrence cases compared with primary cases.
Conclusions:
These observations suggested that patients with MC, CCC and recurrence of all histological type may potentially benefit from future clinical trials of HER3-directed therapies.
Insights
Human epidermal growth factor receptor 3 (HER3) is expressed in over half of epithelial ovarian cancer (EOC) cases, particularly in mucinous and clear cell subtypes. HER3 expression may indicate potential benefit from future HER3-targeted therapies in EOC patients.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Human epidermal growth factor receptor 3 (HER3) is a member of the HER family of tyrosine kinases and a validated target in cancer therapy.
- The development of anti-HER3 antibody-drug conjugates (ADCs) highlights the therapeutic potential of targeting HER3.
- Understanding HER3 expression in epithelial ovarian cancer (EOC) is crucial for evaluating its role in disease progression and potential treatment strategies.
Purpose of the Study:
- To investigate the expression levels of HER3 in a cohort of epithelial ovarian cancer (EOC) patients.
- To analyze the correlation between HER3 expression and various clinicopathological features of EOC.
- To assess the association between HER3 expression and patient prognosis, including progression-free survival (PFS) and overall survival (OS).
Main Methods:
- Immunohistochemistry (IHC) was employed to evaluate HER3 expression in tumor samples from 202 EOC patients.
- Clinicopathological data, including disease stage, surgical outcomes, and tumor markers (e.g., CA125), were collected and analyzed.
- Statistical methods were used to determine the association between HER3 expression, clinicopathological variables, and survival outcomes.
Main Results:
- HER3 expression (IHC score ≥1+) was detected in 55.4% of all EOC cases.
- Higher HER3 expression rates were observed in clear cell carcinoma (78.0%) and mucinous carcinoma (87.9%).
- HER3 expression was associated with early disease stage, successful primary debulking surgery, absence of residual tumor, and lower CA125 levels. HER3 no-expression correlated with shorter PFS. In mucinous carcinoma, HER3 expression was linked to poorer PFS and OS. HER3 expression levels showed a tendency to increase from primary to recurrent tumors.
Conclusions:
- Patients with mucinous carcinoma, clear cell carcinoma, and recurrent EOC may represent a patient population that could benefit from HER3-directed therapies.
- The dynamic nature of HER3 expression between primary and recurrent tumors warrants further investigation.
- HER3 expression status is a relevant biomarker for stratifying EOC patients for targeted treatment trials.
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