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

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.

Immunohistochemical analysis of C/EBPα in non-small cell lung cancer reveals frequent down-regulation in stage II and IIIA tumors: A correlative study of E3590

“…Among the 164 patients analyzed in the current study, the median overall survival of 40.3 months and median disease-free survival of 30.6 months were not different from those of the complete study group and its ancillary laboratory study (7,31).…”

“…217 patients were registered onto the laboratory correlative study. However, 20 samples were never submitted (7). Of the 197 samples available, 164 contained sufficient material for immunohistochemical analysis of C/EBPα expression.…”

“…Survival data for patients enrolled in E3590 and E4592 have been reported previously (7,31). Of the original 488 patients of E3590, median follow up is close to 10 years.…”

“…The overall 5-year survival improvement in these studies ranged from 5 to 15% (3,4,6). Despite the recognized association of clinical and pathologic characteristics (age, weight loss, performance status, tumor-node-metastasis staging system) with prognosis, these parameters alone do not predict which patients are prone to develop recurrent disease and do not identify patients who will benefit from adjuvant therapy (2,4,7). The search for novel prognostic and predictive markers is essential to improve patient selection in early-stage NSCLC for adjuvant treatment strategies, as well as for the discovery of new therapeutic targets.…”

“…The few studies that employed well-established prospective databases of patients with resected NSCLC have frequently shown a lack of significant prognostic information. As an example, mutations in the K-ras oncogene (implicated in signal transduction pathways) and the p53 tumor suppressor gene (involved in cell-cycle regulation) were not associated with significant prognostic significance in the context of a clinical trial of adjuvant therapy for completely resected NSCLC (7). Recent studies of factors involved in metastatic potential, such as vascular endothelial growth factor (VEGF) (14), as well as recently identified transcription factors, such as early growth response gene 1 (EGR1) (15), and cytokines (16) have suggested new prognostic markers in early-stage NSCLC.…”