Lack of prognostic significance of p53 and K-ras mutations in primary resected non-small-cell lung cancer on E4592: a Laboratory Ancillary Study on an Eastern Cooperative Oncology Group Prospective Randomized Trial of Postoperative Adjuvant Therapy.

Abstract

PURPOSE:

To determine the prognostic and predictive significance of p53 and K-ras mutations in patients with completely resected non-small-cell lung cancer (NSCLC).

PATIENTS AND METHODS:

Patients were randomized preoperatively to receive adjuvant postoperative radiotherapy (Arm A) or radiotherapy plus concurrent chemotherapy (Arm B). p53 protein expression was studied by immunohistochemistry (IHC) and p53 mutations in exons 5 to 8 were evaluated by single-strand conformational analysis. K-ras mutations in codons 12, 13, and 61 were determined using engineered restriction fragment length polymorphisms.

RESULTS:

Four hundred eighty-eight patients were entered onto E3590; 197 tumors were assessable for analysis. Neither presence nor absence of p53 mutations, p53 protein expression, or K-ras mutations correlated with survival or progression-free survival. There was a trend toward improved survival for patients with wildtype K-ras (median, 42 months) compared with survival of patients with mutant K-ras who were randomized to chemotherapy plus radiotherapy (median, 25 months; P = .09). Multivariate analysis revealed only age and tumor stage to be significant prognostic factors, although there was a trend bordering on statistical significance for K-ras (P = .066). Analysis of survival difference by p53 by single-stranded conformational polymorphism and IHC, interaction of p53 and K-ras, interaction of p53 and treatment arm, nodal station, extent of surgery, weight loss, and histology did not reach statistical significance.

CONCLUSION:

p53 mutations and protein overexpression are not significant prognostic or predictive factors in resected stage II or IIIA NSCLC. K-ras mutations may be a weak prognostic marker. p53 or K-ras should not be routinely used in the clinical management of these patients.

• Authors: J H Schiller, S Adak, R H Feins, S M Keller, W A Fry, R B Livingston, M E Hammond, B Wolf, L Sabatini, J Jett, L Kohman, D H Johnson
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 19 Issue 2 Pg. 448-57 (Jan 15 2001) ISSN: 0732-183X [Print] United States
• PMID: 11208838 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Topics

• Carcinoma, Non-Small-Cell Lung (genetics, mortality, pathology, therapy)
• Combined Modality Therapy
• DNA Mutational Analysis
• Genes, p53
• Genes, ras
• Humans
• Immunohistochemistry
• Lung Neoplasms (genetics, mortality, pathology, therapy)
• Multivariate Analysis
• Mutation
• Neoplasm Staging
• Polymerase Chain Reaction
• Polymorphism, Restriction Fragment Length
• Polymorphism, Single-Stranded Conformational
• Prognosis
• Proportional Hazards Models
• Prospective Studies
• Survival Analysis