Prognostic significance of K-ras, p53, bcl-2, PCNA, CD34 in radically resected non-small cell lung cancers

Eur J Cancer. 2003 Jun;39(9):1242-50. doi: 10.1016/s0959-8049(03)00232-6.


The aim of this study was to investigate the prognostic significance of a panel of biological parameters in patients with radically resected non-small cell lung cancers (NSCLC). 269 cases with pathological stage I-IIIA NSCLC were retrospectively analysed. Immunohistochemistry was performed to detect protein expression of p53, bcl-2, proliferating cell nuclear antigen (PCNA) and CD34. Polymerase chain reaction (PCR)/direct nucleotide sequencing method was used to detect mutations in K-ras (codons 12, 13, 61, exons 1-2). The Kaplan-Meier estimates of survival were calculated for clinical and biological variables using the Cox model for multivariate analysis. Histological subtype and the pathologic tumour extension (pT) were the most powerful clinical-pathological prognostic factors for survival (P=0.030 and P=0.031, respectively), whereas among the biological parameters, p53 overexpression (P=0.032) and K-ras mutation (P=0.078) had a negative prognostic role, as demonstrated by multivariate analysis. Conversely, bcl-2, PCNA and CD34 expression were not correlated with survival. Statistically significant associations between p53 expression and the squamous cell carcinoma (SCC) subtype, bcl-2 expression and SCC subtype, K-ras mutation and p53 negative expression, p53 and bcl-2, bcl-2 and PCNA overexpression were observed. In conclusion, some biological characteristics such as the K-ras and p53 status may provide useful prognostic information in resected NSCLC patients, in addition to the classical clinico-pathological parameters. However, further studies are needed to clarify the value of adopting biological prognostic factor into clinical practice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD34 / analysis
  • Carcinoma, Non-Small-Cell Lung / chemistry*
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Carcinoma, Squamous Cell / chemistry
  • Carcinoma, Squamous Cell / surgery
  • Female
  • Genes, bcl-2
  • Genes, p53
  • Genes, ras
  • Humans
  • Immunohistochemistry / methods
  • Lung Neoplasms / chemistry*
  • Lung Neoplasms / surgery
  • Male
  • Middle Aged
  • Neoplasm Proteins / analysis*
  • Nucleic Acid Amplification Techniques
  • Prognosis
  • Proliferating Cell Nuclear Antigen / analysis
  • Proportional Hazards Models
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Retrospective Studies
  • Survival Analysis
  • Tumor Suppressor Protein p53 / analysis


  • Antigens, CD34
  • Neoplasm Proteins
  • Proliferating Cell Nuclear Antigen
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53