title: p53 expression and cell proliferation as prognostic factors in laryngeal squamous cell carcinoma.
abstract: OBJECTIVE
  To investigate the prognostic significance of p53 expression and proliferation markers in primary laryngeal squamous cell carcinoma.
  
  
  METHODS
  Primary tumors for analyses were obtained from 103 patients, with complete follow-up data. All patients were treated between the years 1975 and 1990. The expression of p53 was analyzed with monoclonal D07 antibody and proliferative activity with Ki-67 (MIB-1) and PCNA (monoclonal 19A2) antibodies. Volume corrected mitotic (M/V) index and histological grade were determined in hematoxylin and cosin-stained slides.
  
  
  RESULTS
  Sixty-eight percent of the tumors overexpressed p53. During a median follow-up of 62 months, 41 (40%) of patients relapsed. In univariate analysis site of the primary tumor, stage, p53 expression, histologic grade, and M/V index were significant predictors of disease-free survival. In multivariate analysis, only M/V index was a statistically significant predictor of disease-free survival. Overall survival was significantly better for those overexpressing p53 (10-year cumulative survival rate 68% v 44%, P = .004). In multivariate analysis, M/ V index (P = .02), p53 (P = .02), and stage (P = .007) were statistically significant predictors of overall survival. When this analysis includes stratification according to the type of treatment received, M/V index (P = .007), stage (P = .0002), and p53 (P = .006) were even more significant predictors of overall survival. No association between p53 status and proliferative activity was found.
  
  
  CONCLUSIONS
  Overexpression of p53 is associated with favorable disease-free and overall survival in laryngeal squamous cell carcinoma. It may also have an independent prognostic value in laryngeal cancer. M/V index, p53 overexpression, and stage predict with significant accuracy the 10-year overall survival.
authors.affiliation: Department of Pathology, University of Kuopio, Finland. pasi.hirvikoski@uku.fi
authors.forename: P
authors.initials: P
authors.lastname: Hirvikoski
authors.forename: E
authors.initials: E
authors.lastname: Kumpulainen
authors.forename: J
authors.initials: J
authors.lastname: Virtaniemi
authors.forename: R
authors.initials: R
authors.lastname: Johansson
authors.forename: H
authors.initials: H
authors.lastname: Haapasalo
authors.forename: S
authors.initials: S
authors.lastname: Marin
authors.forename: P
authors.initials: P
authors.lastname: Halonen
authors.forename: H
authors.initials: H
authors.lastname: Helin
authors.forename: H
authors.initials: H
authors.lastname: Raitiola
authors.forename: J
authors.initials: J
authors.lastname: Pukander
authors.forename: P
authors.initials: P
authors.lastname: Kellokumpu-Lehtinen
authors.forename: V M
authors.initials: VM
authors.lastname: Kosma
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000473:pathology*; D002455:Cell Division; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007822:Laryngeal Neoplasms / Q000737:chemistry* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D016016:Proportional Hazards Models; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53