Expression of DNA Translesion Synthesis Polymerase η in Head and Neck Squamous Cell Cancer Predicts Resistance to Gemcitabine and Cisplatin-Based Chemotherapy

Purpose: The development of resistance against anticancer drugs has been a persistent clinical problem for the treatment of locally advanced malignancies in the head and neck mucosal derived squamous cell carcinoma (HNSCC). Recent evidence indicates that the DNA translesion synthesis (TLS) polymerase eta (Pol eta; hRad30a gene) reduces the effectiveness of gemcitabine/cisplatin. The goal of this study is to examine the relationship between the expression level of Pol eta and the observed resistance against these chemotherapeutic agents in HNSCC, which is currently unknown. Methods: Sixty-four mucosal derived squamous cell carcinomas of head and neck (HNSCC) from 1989 and 2007 at the City of Hope National Medical Center (Duarte, CA) were retrospectively analyzed. Pretreatment samples were immunostained with anti-Pol eta antibody and the correlation between the expression level of Pol eta and clinical outcomes were evaluated. Forty-nine cases treated with platinum (n=40) or gemcitabine (n=9) based chemotherapy were further examined for Pol eta expression level for comparison with patient response to chemotherapy. Results: The expression of Pol eta was elevated in 67% of the head and neck tumor samples. Pol eta expression level was significantly higher in grade 1 to grade 2 tumors (well to moderately differentiated). The overall benefit rate (complete response+ partial response) in patients treated with platinum and gemcitabine based chemotherapy was 79.5%, where low Pol eta level was significantly associated with high complete response rate (p=0.03), although not associated with overall survival. Furthermore, no significant correlation was observed between Pol eta expression level with gender, age, tobacco/alcohol history, tumor stage and metastatic status. Conclusions: Our data suggest that Pol eta expression may be a useful prediction marker for the effectiveness of platinum or gemcitabine based therapy for HNSCC.