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/EBPα 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/EBPα tumor staining was compared to that of basal bronchial cells (3+). 0 or 1+ (weak) suggested lack of, while 2 or 3+ (strong) suggested C/EBPα expression. Results Ninety tumors (55%) had 0 or 1+ C/EBPα staining, and the remaining 74 (45%) 2 or 3+. Patients with squamous cell carcinomas had a higher percentage of weak C/EBPα IHC staining compared to other histologies (p=0.048) and there was a trend for loss of C/EBPα in poorly differentiated compared to well differentiated tumors (p=0.07). There was no association between C/EBPα IHC and mutations in p53 or K-ras. The median disease-free survival for patients with weak and strong C/EBPα 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/EBPα 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/EBPα is a common event in NSCLC, further elucidation of the involvement of C/EBPα in the pathogenesis and progression of lung cancer may identify novel therapeutic targets.