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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

From the William S. Middleton Veterans Administration Hospital and University of Wisconsin, Madison; University of Wisconsin, Milwaukee, WI; Eastern Cooperative Oncology Group, Dana-Farber Cancer Institute, Boston, MA; University of Rochester Cancer Center, Rochester; Beth Israel Medical Center, New York; Albany Medical Center, Albany; State University of New York, Syracuse, NY; Evanston Hospital, Evanston, IL; University of Washington, Seattle, WA; Latter-Day Saints Hospital and University of Utah School of Medicine, Salt Lake City, UT; Mayo Clinic, Rochester, MN; and Vanderbilt University Medical School, Nashville, TN.

Address reprint requests to Joan H. Schiller, MD, University of Wisconsin, Department of Medicine, Medical Oncology Section, K4/666 Clinical Science Center, 600 Highland Ave, Madison, WI 53792; email jhschill{at}facstaff.wisc.edu

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.

The contents of this study are solely the responsibility of the authors and do not represent the official views of the National Cancer Institute.

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