Correlation between human epidermal growth factor receptor family (EGFR, HER2, HER3, HER4), phosphorylated Akt (P-Akt), and clinical outcomes after radiation therapy in carcinoma of the cervix

OBJECTIVE: To investigate prognostic significance of and correlations between HER1 (EGFR), HER2 (c-erb-B2), HER3 (c-erb-B3), HER4 (c-erb-B4), and phosphorylated Akt (P-Akt) in patients treated with radiation for cervical carcinoma. METHODS: Fifty-five patients with stages I-IVA cervical carcinoma were treated with definitive radiotherapy. Tumor expression of each biomarker was quantitatively scored by an automated immunohistochemical imaging system. Parametric correlations were performed between biomarkers. Univariate and multivariate analysis was performed with disease-free survival (DFS) and overall survival (OS) as primary endpoints. RESULTS: Correlations were observed between expression of HER2 and HER4 (P = 0.003), and HER3 and HER4 (P = 0.004). Decreased HER2, HER4, and P-Akt expressions were significant for diminished DFS on univariate analysis (P = 0.04, P = 0.008, and P = 0.02, respectively). Increased EGFR, and diminished HER2, HER4, and P-Akt expression were significant or showed trends toward significance for diminished OS on univariate analysis (P = 0.07, P = 0.008, P = 0.09, and P = 0.08, respectively). After controlling for pretreatment factors, multivariate analysis revealed HER2 associated with improved OS (P = 0.05). CONCLUSIONS: These data emphasize that significant correlations exist between the differential expression of various HER family receptors. Multivariate analysis revealed only increased HER2 expression associated with improved OS after controlling for pretreatment clinical factors. These data emphasize the importance of continued basic and translational research on the HER family of receptors in cervical carcinoma.