Prognostic significance of mutant p53 protein, P-glycoprotein and glutathione S-transferase-pi in patients with unresectable non-small cell lung cancer

Anticancer Res. May-Jun 2003;23(3C):2829-36.

Abstract

Background: The prognostic significance of mutant p53 protein, p-glycoprotein (P-gp) and glutathione S-transferase-pi (GST-pi) in patients with unresectable non-small cell lung cancer (NSCLC) has not been established.

Materials and methods: We performed immunohistochemical staining of p53, P-gp and GST-pi using transbronchial biopsy specimens obtained from previously untreated NSCLC patients.

Results: Of 45 patients examined, p53 immunostaining was positive in 18 (40%) patients. The objective response rate by cisplatin (CDDP)-based chemotherapy was significantly lower in patients with p53-positive tumors compared to those with p53-negative tumors (22% versus 59%, p = 0.0143). Survival of the patients with p53-positive tumors was significantly shorter than those with p53-negative tumors (median survival time: 4.6 months versus 12.2 months, p = 0.011), which was confirmed by the multivariate analysis (p = 0.0243). However, P-gp and GST-pi showed no significant relationship with either response rate or survival in patients with unresectable NSCLC receiving CDDP-based chemotherapy.

Conclusion: p53 alteration is an independent and significant indicator to predict unfavorable prognosis in patients with unresectable NSCLC.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / biosynthesis
  • ATP Binding Cassette Transporter, Subfamily B / genetics*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Biopsy
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cisplatin / administration & dosage
  • Female
  • Glutathione Transferase / biosynthesis
  • Glutathione Transferase / genetics*
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Mutation*
  • Prognosis
  • Retrospective Studies
  • Survival Rate
  • Tumor Suppressor Protein p53 / biosynthesis
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • ATP Binding Cassette Transporter, Subfamily B
  • Tumor Suppressor Protein p53
  • Glutathione Transferase
  • Cisplatin