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

Purpose: To determine the prognostic and predictive significance of p53 and K-ras mutations in patients with completely resected non-small-cell lung c ancer (NSCLC). Patients and Methods: Patients were randomized preoperatively to receive ad juvant postoperative radiotherapy (Arm A) or radiotherapy plus concurrent c hemotherapy (Arm 8). p53 protein expression was studied by immunohistochemi stry (IHC) and p53 mutations in exons 5 to 8 were evaluated by single-stran d conformational analysis. K-ras mutations in codons 12, 13, and 61 were de termined using engineered restriction fragment length polymorphisms. Results: Four hundred eighty-eight patients were entered onto E3590; 197 tu mors were assessable for analysis. Neither presence nor absence of p53 muta tions, p53 protein expression, or K-ras mutations correlated with survived ar progression-free survival. There was a trend toward improved survival fo r patients with wildtype K-ras (median, 42 months) compared with survival o f patients with mutant K-ros who were randomized to chemotherapy plus radio therapy (median, 25 months; P =.09), Multivariate analysis revealed only ag e 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 polymorphi sm 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 r each statistical significance. Conclusion: p53 mutations and protein overexpression are not significant pr ognostic or predictive factors in resected stage II or IIIA NSCLC. K-ros mu tations may be a weak prognostic marker. p53 or K-ras should nat be routine ly used in the clinical management of these patients. J Clin Oncol 19:448-4 57. (C) 2001 by American Society of Clinical Oncology.