title: Expression of DNA translesion synthesis polymerase η in head and neck squamous cell cancer predicts resistance to gemcitabine and cisplatin-based chemotherapy.
abstract: OBJECTIVE
  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 η (Pol η; hRad30a gene) reduces the effectiveness of gemcitabine/cisplatin. The goal of this study is to examine the relationship between the expression level of Pol η 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 η antibody and the correlation between the expression level of Pol η and clinical outcomes were evaluated. Forty-nine cases treated with platinum (n=40) or gemcitabine (n=9) based chemotherapy were further examined for Pol η expression level for comparison with patient response to chemotherapy.
  
  
  RESULTS
  The expression of Pol η was elevated in 67% of the head and neck tumor samples. Pol η 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 η 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 η expression level with gender, age, tobacco/alcohol history, tumor stage and metastatic status.
  
  
  CONCLUSIONS
  Our data suggest that Pol η expression may be a useful prediction marker for the effectiveness of platinum or gemcitabine based therapy for HNSCC.
authors.affiliation: Department of Pathology, St. Luke's-Roosevelt Hospital Center, Affiliated Hospital of Columbia University College of Physicians and Surgeons, New York, New York, United States of America.
authors.forename: Wendi
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Yih-wen
authors.initials: YW
authors.lastname: Chen
authors.affiliation: Department of Molecular Pharmacology, Beckman Research Institute of the City of Hope National Medical Center, Duarte, California, United States of America.
authors.forename: Xiyong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pathology, City of Hope Comprehensive Cancer Center, Duarte, California, United States of America.
authors.forename: Peiguo
authors.initials: P
authors.lastname: Chu
authors.affiliation: Department of Pathology, City of Hope Comprehensive Cancer Center, Duarte, California, United States of America.
authors.forename: Sofia
authors.initials: S
authors.lastname: Loria
authors.affiliation: Department of Molecular Pharmacology, Beckman Research Institute of the City of Hope National Medical Center, Duarte, California, United States of America.
authors.forename: Yafan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Molecular Pharmacology, Beckman Research Institute of the City of Hope National Medical Center, Duarte, California, United States of America.
authors.forename: Yun
authors.initials: Y
authors.lastname: Yen
authors.affiliation: Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Kai-Ming
authors.initials: KM
authors.lastname: Chou
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D000077195:Squamous Cell Carcinoma of Head and Neck; D000093542:Gemcitabine; D000099270:Y-Family DNA Polymerases
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin; D004259:DNA-Directed DNA Polymerase; D003841:Deoxycytidine; D000093542:Gemcitabine; C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases