Prognostic value of immunohistochemical expressions of p53, HER-2/neu, and bcl-2 in stage I non-small-cell lung cancer

Hum Pathol. 2002 Jan;33(1):105-10. doi: 10.1053/hupa.2002.30183.

Abstract

The outcomes of patients with stage I non-small-cell lung cancer (NSCLC) vary greatly, with a 5-year survival rate of approximately 60%. This study evaluated a number of molecular markers that may aid in predicting prognosis in stage I NSCLC after surgical resection. Immunohistochemical (IHC) staining of p53, HER-2/neu, bcl-2 proteins was performed on paraffin-embedded sections from 85 stage I NSCLC patients who underwent surgery and were followed up for 32 to 44 (median, 39.0; mean, 37.1) months postoperatively. Differences in survival rates were evaluated by log rank test. The prevalence of p53, HER-2/neu, and bcl-2 expression in stage I NSCLC is 59%, 29%, and 46%, respectively. HER-2/neu expression is seen more frequently in adenocarcinomas, and bcl-2 is seen more frequently in squamous carcinomas. p53 and HER-2/neu expression in stage I NSCLC is associated with significantly short survival. Patients whose tumors were both p53 and HER-2/neu positive had the worst outcome, with a survival rate of only 20%, compared with 80% in those whose tumors were both p53 and HER-2/neu negative (P = .0003). The survival rates were 54% in patients who were p53 positive but HER-2/neu negative and 50% in those who were in p53 negative, HER-2/neu positive. The differences among these 4 groups were statistically significant (P =.001). Bcl-2 does not seem to be a prognostic factor for survival. Multivariate analysis showed that overexpression of p53 and HER-2/neu, presence of angiolymphatic invasion, and tumor size > 3.0 cm were independent factors predicting poor survival. p53 and HER-2/neu by IHC staining appear to be valuable prognostic markers in stage I NSCLC patients after surgery. The worst outcome was seen in patients who expressed both p53 and HER-2/neu, suggesting that these patients might benefit from additional adjuvant therapy.

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Aged
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
  • Receptor, ErbB-2 / biosynthesis*
  • Survival Rate
  • Tumor Suppressor Protein p53 / biosynthesis*

Substances

  • Biomarkers, Tumor
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53
  • Receptor, ErbB-2