title: Epidermal growth factor receptor, p53 mutation, and pathological response predict survival in patients with locally advanced esophageal cancer treated with preoperative chemoradiotherapy.
abstract: OBJECTIVE
  Despite the availability of cellular markers associated with cell cycle, apoptosis, and DNA repair, predictive factors for pathological complete response (CR) and overall survival (OS) are few in patients with locally advanced esophageal cancer. This study evaluates the role of clinical and cellular markers in predicting CR and OS in patients with esophageal cancer.
  
  
  METHODS
  Patients were treated with infusional cisplatin and 5-fluorouracil combined with daily radiotherapy followed by esophagectomy. Pretreatment tumors (n = 54) were analyzed for epidermal growth factor receptor (EGF-R), bax, and bcl-2 expression by immunohistochemistry and for p53 mutations by direct DNA sequencing of exons 5-8. Clinical covariates included patients' age at enrollment; gender; Barrett's metaplasia; and tumor location, histology, and differentiation. Logistic regression and survival analyses were used to evaluate the predictors.
  
  
  RESULTS
  Age ranged from 32 to 75 years; most patients were male (45 male; 9 female); and tumors were distal (47 distal; 7 mid), adenocarcinoma (41 adenocarcinomas; 13 squamous cell carcinomas), and moderately differentiated (33 moderate; 6 well; 15 poor). Female gender predicted CR (odds ratio 7.5; 95% confidence interval, 1.4-41). The OS was 43% at 5 years. Presence of CR (P < 0.001 log rank) and p53 mutation (P = 0.051 log rank) correlated with increased OS, whereas increased EGF-R expression predicted poor OS (P = 0.009 log rank). EGF-R remained significant when adjusted for clinical covariates. There was a trend toward increased OS related to better tumor differentiation and decreased bcl-2.
  
  
  CONCLUSIONS
  These data suggest that EGF-R and p53 mutation may be used as both outcome predictors and targets for molecular therapy for esophageal cancer.
authors.affiliation: Division of Medical Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231, USA. gibsomi@jhmi.edu
authors.forename: Michael K
authors.initials: MK
authors.lastname: Gibson
authors.forename: Susan C
authors.initials: SC
authors.lastname: Abraham
authors.forename: Tsung-Teh
authors.initials: TT
authors.lastname: Wu
authors.forename: Barbara
authors.initials: B
authors.lastname: Burtness
authors.forename: Richard F
authors.initials: RF
authors.lastname: Heitmiller
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Heath
authors.forename: Arlene
authors.initials: A
authors.lastname: Forastiere
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism; D000368:Aged; D002945:Cisplatin / Q000627:therapeutic use; D003131:Combined Modality Therapy; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000096:biosynthesis*; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000628:therapy*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012044:Regression Analysis; D013997:Time Factors; D016896:Treatment Outcome; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D066246:ErbB Receptors; D002945:Cisplatin; D005472:Fluorouracil