ErbB3, a possible prognostic factor of head and neck squamous cell carcinoma

Abstract

Objective. We aimed to identify the prognostic factors in head and neck squamous cell carcinoma (HNSCC) by using gene expression analysis and candidate biomarkers for adjuvant therapy. Study Design. Complementary DNA (cDNA) microarray analysis was performed by using samples from 8 patients, who had died as a result of fulminant recurrence shortly after postoperative radiation therapy, and the results were compared with those from patients with HNSCC of similar stage, but without recurrence. Tissue microarray and immunohistochemistry of samples from 69 patients with oral cavity squamous cell carcinoma indicated ErbB3 to be a prognostic marker, and its expression was analyzed in the HNSCC cell lines. Sapitinib was tested as a concurrent inhibitor of EGFR, ErbB2, and ErbB3. In 15 mice, tumor xenograft was implanted at the lateral tongue, and tumor growth was evaluated. Results. ErbB3 overexpression in patients with treatment-resistant HNSCC was associated with relapse-free survival, disease-free survival, and overall survival (P = .018, P = .006, and P = .003, respectively). In the HNSCC cell line, ErbB2 and ErbB3 overexpression was inhibited by postoperative adjuvant therapy with sapitinib, which was also seen to improve survival in an animal model. Conclusions. ErbB3 overexpression predicts a poor clinical outcome. Sapitinib was shown to be an effective inhibitor in the HNSCC cell line and animal models of cancer but with no statistical significance. Further studies with larger groups are needed to better support these results.