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

Abstract

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.

Molecular Profiling of Computed Tomography Screen-Detected Lung Nodules Shows Multiple Malignant Features

“…In agreement with the aforementioned cDNA study, the almost identical percentages of molecular alterations reported herein support the hypothesis that lung cancer detected in a screening program has a similar malignant potential than conventionally, nonscreen-detected cancer. Furthermore, all the data from both series are concordant with the published literature on resectable non -small cell lung cancer in relation to cell cycle -related proteins (18,21,23,24,33,(40)(41)(42), apoptosis regulators (26,43,44), invasive and angiogenic markers (26,27), RNA processing molecules (28,29), and genetic aberrations (15,38).…”

Overexpression of S100A2 protein as a prognostic marker for patients with stage I non small cell lung cancer

“…2 Several immunocytochemical markers have already been identified as prognostic indicators in patients with early-stage NSCLC, including K-ras/p21, p53, C-erbB-2/p185, bcl-2, Rb and Ki-67 proteins. [3][4][5][6][7][8] Some molecules have also been evaluated at the mRNA level for their prognostic value, including retinoic acid receptor B, cyclooxygenase 2, vascular endothelial growth factor, matrix metalloproteinase 2 and 9, E-cadherin, angiopoietin 2 and CD44. [9][10][11][12][13] In addition, recent methylation analyses of the promoter regions in various genes, including DAP, GSTP1, APC and MGMT, have shown that hypermethylation of these genes may indicate a biologically aggressive tumor in patients with stage I NSCLC.…”

Pharmacogenetics of Anticancer Drug Sensitivity in Non-Small Cell Lung Cancer

“…Waf1/Cip1 overexpression may be associated with a less aggressive tumor behavior (Kalomenidis et al, 2001). In surgical samples of NSCLC, detectable Bcl-2 was shown by immunohistochemistry in 20 of 107 (19%) cases and this finding was associated with squamous cell histology.…”