title: Prognostic role of p53 protein expression in epidermoid carcinoma of the anal canal.
abstract: OBJECTIVE
  To assess the prognostic significance of p53 protein expression in patients with primary epidermoid carcinoma of the anal canal managed by radiation therapy (XRT), 5-fluorouracil (5-FU), and mitomycin C (MMC).
  
  
  METHODS
  From January 1991 to December 1993, 58 consecutive patients with primary epidermoid carcinoma of the anal canal were treated in a prospectively designed protocol of XRT (24 Gy/12--3(1/2) wk split--28 Gy/14) and concurrent 5-FU (1000 mg/m2/day 1-4) and MMC (10 mg/m2 day 1) of each cycle of XRT. Paraffin-embedded tumor samples were unavailable in 9 patients, leaving 49 patients in the study. Expression of p53 protein was studied using immunohistochemistry and quantified as percent tumor nuclei showing positive staining. Actuarial survival and disease-free survival (DFS) rates were estimated by the Kaplan-Meier method, and compared using the log-rank test. A Cox proportional hazard model was used for the multivariable analysis.
  
  
  RESULTS
  There were 6 T1, 26 T2, 7 T3, and 10 T4 lesions. Primary tumor sizes ranged from 1-15 cm with a median of 4 cm. There were 6 patients with nodal metastases. Median follow-up was 4.5 years. Positive nuclear immunostaining for p53 was observed in 40 of 49 patients. The median percent positive staining was 5%, with 13, 9, and 18 patients showing staining in <5%, 5 to <10%, and 10-50% of tumor nuclei respectively. There was no correlation of percent p53 staining with gender, age, tumor stage, size, or histology. Local, regional, and distant failures were observed in 12, 2, and 2 patients respectively. The 5-yr survival and DFS were 84% and 64% respectively. In univariate analysis, the only prognostic variable for survival was gender. For DFS, advanced T category and large tumor size were predictive of poor DFS. In multivariate analysis, poor DFS was associated with high T category (p = 0.0008), basaloid histology (p = 0.001), male gender (p = 0.002), and increasing percent of p53 protein expression (p = 0.01).
  
  
  CONCLUSIONS
  It is concluded that expression for p53 protein is present in a high percentage of patients with epidermoid carcinoma of the anal canal. For patients managed with combined XRT, 5-FU, and MMC, percent p53 protein expression is of prognostic value for DFS independent of other clinical factors such as T category, gender, and histology.
authors.affiliation: Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Ontario, Canada.
authors.forename: C S
authors.initials: CS
authors.lastname: Wong
authors.forename: M S
authors.initials: MS
authors.lastname: Tsao
authors.forename: V
authors.initials: V
authors.lastname: Sharma
authors.forename: W B
authors.initials: WB
authors.lastname: Chapman
authors.forename: M
authors.initials: M
authors.lastname: Pintilie
authors.forename: B J
authors.initials: BJ
authors.lastname: Cummings
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001005:Anus Neoplasms / Q000737:chemistry* / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy; D003131:Combined Modality Therapy; D016228:Endothelial Growth Factors / Q000032:analysis; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008222:Lymphokines / Q000032:analysis; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000032:analysis*; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D008222:Lymphokines; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016685:Mitomycin; D005472:Fluorouracil