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ErbB-3 predicts survival in ovarian cancer
Berno Tanner1, Dirk Hasenclever, Katja Stern
1Department of Gynecology and Obstetrics, University of Mainz, Mainz, Germany.
Background:
HER3 (erbB-3) is a member of the epidermal growth factor receptor (EGFR) family. After dimerization with other members of the EGFR family several signal transduction cascades can be activated, including phosphoinosite 3'-kinase (PI3-K)/Akt and extracellular signal-regulated kinase (ERK1/2). Here, we studied a possible association between HER3 expression and prognosis in patients with ovarian cancer.
Methods:
Tumor tissue of 116 consecutive patients diagnosed with primary epithelial ovarian cancer between 1986 and 1995 was analyzed immunohistochemically for HER3 expression. A possible influence of HER3 expression on survival was studied by multivariate Cox regression adjusting for established clinical prognostic factors.
Results:
A positive HER3 expression was observed in 53.4% of the patients. HER3 expression was associated with decreased survival in proportional hazard modeling, including the International Federation of Gynecology and Obstetrics (FIGO) stage, histologic grade and type, residual disease, and age. After likelihood ratio forward as well as backward selection, only HER3 expression (hazard ratio, 1.71; 95% CI, 1.10 to 2.67; P = .018), FIGO stage (hazard ratio, 4.78; 95% CI, 1.89 to 12.08; P = .001), residual tumor (hazard ratio, 2.69; 95% CI, 1.40 to 5.17; P = .003), and age (hazard ratio, 2.06; 95% CI, 1.17 to 3.65; P = .013) were found to be significant. Kaplan-Meier plots demonstrated a clear influence of HER3 expression on survival time. Median survival time was 3.31 years (95% CI, 1.93 to 4.68) for patients with low HER3 expression, compared with only 1.80 years (95% CI, 0.83 to 2.78) for patients with HER3 overexpression (log-rank test P = .0034).
Conclusion:
HER3 may represent a new prognostic factor in primary epithelial ovarian cancer. Pending validation, exploration of therapeutic strategies to block HER3 could be warranted.
Insights
High HER3 (human epidermal growth factor receptor 3) expression in ovarian cancer patients is linked to poorer survival outcomes. This finding suggests HER3 may serve as a new prognostic marker for epithelial ovarian cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- HER3 (human epidermal growth factor receptor 3) is a key member of the epidermal growth factor receptor (EGFR) family.
- HER3 activation, through dimerization with other EGFR family members, triggers critical signaling pathways like PI3-K/Akt and ERK1/2, influencing cell growth and survival.
Purpose of the Study:
- To investigate the potential association between HER3 expression levels and the prognosis of patients diagnosed with primary epithelial ovarian cancer.
- To determine if HER3 expression serves as an independent prognostic factor in ovarian cancer.
Main Methods:
- Immunohistochemical analysis of HER3 expression in tumor tissues from 116 primary epithelial ovarian cancer patients.
- Multivariate Cox regression analysis was employed to assess the impact of HER3 expression on survival, adjusting for established prognostic factors such as FIGO stage, histologic grade, residual disease, and age.
Main Results:
- Positive HER3 expression was detected in 53.4% of the studied ovarian cancer cases.
- HER3 expression was significantly associated with decreased patient survival (hazard ratio, 1.71; P = .018), independent of FIGO stage, residual tumor, and age.
- Patients with HER3 overexpression exhibited a median survival of 1.80 years compared to 3.31 years for those with low HER3 expression (log-rank test P = .0034).
Conclusions:
- HER3 expression emerges as a significant new prognostic factor in primary epithelial ovarian cancer.
- Further research and validation are recommended to explore therapeutic strategies targeting HER3 blockade for ovarian cancer treatment.
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