Expression of ERCC1, RRM1 and class III beta-tubulin in head and neck cancer and its clinical significance

Abstract

Introduction: Management of head and neck cancer (HNCa) is very complicated, as surgery is limited by the anatomical extent of tumor and the desire to preserve essential organs. To achieve the optimal effects, additional therapeutic options based on molecular tumor profiling have been increasingly tried in HNCa. This study explored biomarker expression profiles of HNCa with the goal of developing therapeutic strategies. Methods: Eighty three patients consisting of 74 cases of squamous cell carcinoma (SCC) and nine cases of undifferentiated carcinoma (UDC) were enrolled. Expression of three selected biomarkers – excision repair cross-complementation group 1 (ERCC1), class III ß-tubulin (TUBB3), and ribonucleotide reductase M1 (RRM1) – previously reported to be indicators of therapeutic responses in non-small cell lung cancer was investigated by immunohistochemistry (IHC) Human papilloma virus (HPV) status was examined by IHC for p16, in situ hybridization (ISH), and DNA chip analysis. Epstein-Barr virus (EBV) was detected by ISH. Results: HPV was detected in 27 of 74 SCC cases, most frequently in the oropharynx (15 of 27 cases). EBV was detected in 11 cases including all nine UDC cases. Expression of the three biomarkers was relatively high throughout the primary location of HNCa, except for laryngeal SCC, which displayed low expression of ERCC1. High expression of ERCC1 was found in 64 of 70 cases of SCC (91.4 %), RRM1 in 56 of 70 cases of SCC (80.0%), and TUBB3 in 37 of 71 cases of SCC (52.1%). Expression of TUBB3 was associated with histologic types. None of the nine cases of UDC expressed high levels of TUBB3 (p=.001). Also, high expression of TUBB3 was an independent predictor of better overall survival in SCC (p=.020). Additionally, positivity of p16 was related to longer disease free survival and overall survival. Conclusions: Unlike lung carcinoma, expression of ERCC1 or RRM1 did not correlate with clinical parameters or HPV status. However, p16 and TUBB3 might be useful predictive biomarkers in HNCa.