title: Markers of radioresistance in squamous cell carcinomas of the head and neck: a clinicopathologic and immunohistochemical study.
abstract: OBJECTIVE
  The lack of accurate criteria to predict the response to radiotherapy for individual patients with squamous cell carcinoma of the head and neck (HN-SCC) remains a major problem. The purpose of this study was to investigate the role of several biologic tumor markers to complement clinical prognostic factors in the assessment of response to radiotherapy in SCCs.
  
  
  METHODS
  p53, ki-67, c-erb B-2, heat-shock protein-27 (HSP-27), and glutathione S transferase (GSTpi) were evaluated by immunohistochemistry on biopsies from 101 patients treated for head and neck cancer by radical radiotherapy. Expression of each marker was correlated with local control and survival using Kaplan-Meier curves. A Cox regression multivariate analysis was also performed that included all clinical and immunohistochemical variables.
  
  
  RESULTS
  Expression of p53 and low cell proliferation allowed identification of patients whose tumors did not respond to radiation. Patients with p53-expressing tumors displayed a relative risk (RR) of 3.78 for not being controlled by radiotherapy compared with patients with p53-negative tumors. For tumors with a high growth fraction (ki-67 > 20%) the RR was 0.25 compared with tumors with a low growth fraction (ki-67 < 20%). When p53 expression and cell proliferation were considered simultaneously in a Cox model, the association with resistance to radiation was significant (P = .000004). The RR for resistance with one (p53 staining or ki-67 < 20%) or two (p53 staining and ki-67 < 20%) unfavorable markers was, respectively, 3.8 and 14.87.
  
  
  CONCLUSIONS
  Patients whose tumor expressed p53 with low growth fraction (ki-67 < 20%) had a strong probability not to respond to radiation therapy. Similarly, absence of p53 expression with a high cell proliferation predicted an excellent outcome after radiotherapy even for patients with advanced disease. Prediction of the outcome of radiotherapy would eventually facilitate the early choice of an adequate treatment.
authors.affiliation: Department of Pathology, Faculté de Médicine, Université Laval, Québec, Canada.
authors.forename: H
authors.initials: H
authors.lastname: Raybaud-Diogène
authors.forename: A
authors.initials: A
authors.lastname: Fortin
authors.forename: R
authors.initials: R
authors.lastname: Morency
authors.forename: J
authors.initials: J
authors.lastname: Roy
authors.forename: R A
authors.initials: RA
authors.lastname: Monteil
authors.forename: B
authors.initials: B
authors.lastname: Têtu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D005982:Glutathione Transferase / Q000032:analysis; D006258:Head and Neck Neoplasms / Q000737:chemistry* / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011836:Radiation Tolerance; D011879:Radiotherapy Dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D005982:Glutathione Transferase; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53