Combined Expression of p53, Bcl-2, and p21WAF-1 Proteins in Lung Cancer and Premalignant Lesions: Association With Clinical Characteristics

Lung. 2001;179(5):265-78. doi: 10.1007/s004080010067.


We examined p53, p21WAF-1, and Bcl-2 protein expression in malignant and nonmalignant bronchial specimens obtained during bronchoscopy from 60 lung cancer patients. Twenty-six (43.3%), 36 (60%), and 20 (33.3%) of the tumors were p53, p21WAF-1, and Bcl-2 positive, respectively. High-level p53 and Bcl-2 expression characterized advanced preneoplastic lesions, while hyperplasias, squamous metaplasias, and mild dysplasias exhibited low levels of expression. There was no difference between early and advanced preneoplastic lesions in the level of p21WAF-1, expression. A history of heavy smoking was associated with p21WAF-1, expression in preneoplastic lesions (p = 0.022) and tumors (p = 0.032). p53(-)/p21WAF-1(++)/bcl-2(-) was the only significant independent predictor of lower clinical stage (OR: 0.88, p = 0.038). In univariate analysis, survival of NSCLC patients was affected by disease stage (p <0.001) and tumor histology (p = 0.018). While single-protein expression was not associated with prognosis, the combined immunophenotype p53(-)/p21WAF-1(++)/bcl-2(-) predicted longer survival (p = 0.03). In multivariate analysis, only the TNM stage was found to be a prognostic factor for NSCLC. We conclude that p53 and Bcl-2 alterations may happen early in bronchial carcinogenesis and that absence of these alterations in combination with p21WAF-1, overexpression may be associated with a less aggressive tumor behavior.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Bronchi / metabolism
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / metabolism*
  • Enzyme Inhibitors / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Precancerous Conditions / metabolism*
  • Precancerous Conditions / mortality
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Smoking / adverse effects
  • Tumor Suppressor Protein p53 / metabolism*


  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Enzyme Inhibitors
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53