High Immunohistochemical Expression of Translesion DNA Synthesis Enzyme Polymerase η in Head and Neck Squamous Cell Cancer Is Associated with Platinum-Based Chemotherapy Resistance
Wendi Zhou, Xiyong Liu, Peiguo Chu, Sofia Loera, Bruce Wenig, Kai-Ming Chou, Yun Yen. St. Luke's - Roosevelt Hospital and Beth Israel Medical Center, New York, NY; City of Hope Comprehensive Cancer Center, Duarte, CA; Indiana University, Indianapolis, IN
Background: The development of cancer drug resistance in mucosal derived squamous cell carcinoma of the head and neck (HNSCC) is a persistent problem limiting the successful treatment of locally advanced malignancies. Recent evidence from basic research indicates that translesion DNA synthesis enzyme polymerase η (pol η; XPV gene) negatively influence the effectiveness of cisplatin by bypassing cisplatin induced DNA adducts, but little is known as to whether the immunostaing level of pol η in HNSCC patient samples is ultimately relevant to tumor chemotherapy sensitivity.
Design: Immunohistochemistry staining for pol η was performed on surgical specimens of sixty-four cases of mucosal derived, locally advanced HNSCC. The correlations of expression level of pol η with patient demographic, tumor staging, histological differentiation, and clinical outcomes were investigated. Expression of pre and post- treatment pol η in relation to chemoresponse was further evaluated in 49 cases treated with platinum-based chemotherapy.
Results: Nuclear Pol η expression was limited at basal layer of benign squamous mucosa. Higher nuclear pol η expression was detected in 65% of SCC. Pol η staining level was negatively associated with tumor grade, but not significantly differed by gender, age, Tobacco/alcohol history, tumor stage and metastatic status. Complete response rate was observed significantly higher in negative/low baseline Pol η staining group (44%, p=0.03). No survival significance was found to be related to Pol η staining level, although there is a trend showing patient with high Pol η expression tends to have shorter overall survival.
Conclusions: Our data, for the first time, provide evidences that in situ pol η staining might be a novel marker of chemoresponse in HNSCC patients receiving platinum-based therapy.
Category: Head & Neck
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 213, Wednesday Morning