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

Purpose: We sought to determine the association of C/EBP alpha expression status with clinical, pathologic and molecular characteristics, as well as outcomes, in non-small-cell lung cancer (NSCLC). This is the first comprehensive study of this transcription factor in patients with NSCLC. Patients and methods: Our cohort originated from ECOG 3590 (randomized trial of postoperative adjuvant therapy with thoracic radiation or cisplatin and etoposide plus thoracic radiation in patients with completely resected stages II and IIIA NSCLC; and its laboratory correlate, ECOG 4592). One hundred and sixty four tumor samples contained sufficient material for immunohistochemical (IHC) analysis. C/EBPa tumor staining was compared to that of basal bronchial cells (3+). 0 or 1+ (weak) suggested tack of, white 2 or 3+ (strong) suggested C/EBP alpha expression. Results: Ninety tumors (55%) had 0 or 1+ C/EBP alpha staining, and the remaining 74 (45%) 2 or 3+. Patients with squamous cell carcinomas had a higher percentage of weak C/EBP alpha IHC staining compared to other histologies to = 0.048) and there was a trend for toss of C/EBP alpha in poorly differentiated compared to welt differentiated tumors (p = 0.07). There was no association between C/EBP alpha IHC and mutations in p53 or K-ras. The median disease-free survival for patients with weak and strong C/EBP alpha. IHC expression was 29.6 and 30.6 months, respectively (p = 0.94). The median overall survival between the weak and strong groups was 43.5 and 38.5 months, respectively (p = 0.83). Conclusions: Loss of expression of C/EBP alpha is seen in over half of stage II and IIIA NSCLC, specifically in squamous cell carcinomas and poorly differentiated tumors. Since down-regulation of C/EBP alpha. is a common event in NSCLC, further elucidation of the involvement of C/EBP alpha in the pathogenesis and progression of lung cancer may identify novel therapeutic targets. (c) 2006 Elsevier Ireland Ltd. All rights reserved.