Prognostic Significance of Mutant p53 Protein, P-glycoprotein and Glutathione S-transferase-π in Patients with Unresectable Non-small Cell Lung Cancer

Background: The prognostic significance of mutant p53 protein, p-glycoprotein (P-gp) and glutathione S-transferase-π (GST-π) 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-π 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-π 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.