title: GP96 is over-expressed in oral cavity cancer and is a poor prognostic indicator for patients receiving radiotherapy.
abstract: BACKGROUND
  Oral cavity cancers (ORC) are the most common cancers, and standard treatment is radical surgery with postoperative radiotherapy. However, locoregional failure remains a major problem, indicating radioresistance an important issue. Our previous work has shown that GP96 contributed to radioresistance in nasopharyngeal and oral cancer cell lines. In this study, we determined clinical significance of GP96 in ORC by evaluation of GP96 expression and its association with disease prognosis in patients receiving radiotherapy
  
  
  METHODS
  Total of 79 ORC patients (77 males, median age: 48 years old) receiving radical surgery and postoperative radiotherapy between Oct 1999 and Dec 2004 were enrolled. Patients in pathological stages II, III and IV were 16.5%, 16.5% and 67%, respectively. For each patient, a pair of carcinoma tissue and grossly adjacent normal mucosa was obtained. GP96-expression was examined by western blot analysis, and the association with clinicopathological status was determined.
  
  
  RESULTS
  Three-year locoregional control (LRC), distant metastasis-free survival (DMFS), disease-specific survival (DSS) and overall survival (OS) rates were 69%, 79%, 63% and 57%, respectively. We found that 55 patients (70%) displayed GP96-overexpression in the tumor tissue, which correlated with a higher pN stage (p = 0.020) and tumor depth (> 10 mm) (p = 0.045). Nodal extracapsular spreading (ECS) and GP96-overexpression predicted adverse LRC (p = 0.049 and p = 0.008). When stratified by nodal ECS, the adverse impact of GP96 remained significant in three-year LRC (p = 0.004). In multivariate analysis, GP96-overexpression was also an independent predictor of LRC, DSS and OS (p = 0.018, p = 0.011 and p = 0.012).
  
  
  CONCLUSIONS
  GP96 may play roles in radioresistance which attributes to tumor invasiveness in oral cancer patients receiving radiotherapy. GP96 may serve as a novel prognostic marker of radiotherapy. However, further independent studies are required to validate our findings in a larger series.
authors: Department of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan.
authors: Chien-Yu
authors: CY
authors: Lin
authors: Ting-Yang
authors: TY
authors: Lin
authors: Hung-Ming
authors: HM
authors: Wang
authors: Shiang-Fu
authors: SF
authors: Huang
authors: Kang-Hsing
authors: KH
authors: Fan
authors: Chun-Ta
authors: CT
authors: Liao
authors: I-How
authors: IH
authors: Chen
authors: Li-Yu
authors: LY
authors: Lee
authors: Yen-Liang
authors: YL
authors: Li
authors: Yin-Ju
authors: YJ
authors: Chen
authors: Ann-Joy
authors: AJ
authors: Cheng
authors: Joseph T
authors: JT
authors: Chang
mesh_terms: D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000502:physiology; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000532:radiotherapy*; D009361:Neoplasm Invasiveness; D049268:Positron-Emission Tomography / Q000379:methods; D011379:Prognosis; D019275:Radiopharmaceuticals / Q000494:pharmacology; D011878:Radiotherapy / Q000379:methods*
chemical_list: D008562:Membrane Glycoproteins; D019275:Radiopharmaceuticals; C053387:endoplasmin; D019788:Fluorodeoxyglucose F18