Cyclooxygenase-2 Overexpression Is a Marker of Poor Prognosis in Stage I Non-Small Cell Lung Cancer

• Published in: Clinical cancer research Vol. 7; no. 4; pp. 861 - 867
• Main Authors: Khuri, F R, Wu, H, Lee, J J, Kemp, B L, Lotan, R, Lippman, S M, Feng, L, Hong, W K, Xu, X C
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.04.2001
• Subjects: Biological and medical sciences; Biomarkers, Tumor - metabolism; Carcinoma, Non-Small-Cell Lung - diagnosis; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - mortality; Cyclooxygenase 2; Humans; Isoenzymes - metabolism; Lung Neoplasms - diagnosis; Lung Neoplasms - metabolism; Lung Neoplasms - mortality; Medical sciences; Membrane Proteins; Neoplasm Staging; Pneumology; Prognosis; Prostaglandin-Endoperoxide Synthases - metabolism; Receptors, Retinoic Acid - metabolism; Survival Analysis; Tumors of the respiratory system and mediastinum; Human; Lung disease; Prostaglandin-endoperoxide synthase; Prognosis; Respiratory disease; Enzyme; Tumoral tissue; Retinoid; Biological marker; Gene overexpression; Malignant tumor; Gene expression; In vitro; Survival; Bronchopulmonary; Clinical stage; Bronchus disease; Oxidoreductases; Predictive factor; Retinoic acid; Subtype; Non small cell carcinoma; Hormonal receptor
• ISSN: 1078-0432; 1557-3265

Cyclooxygenase-2 (COX-2), the enzyme that converts arachidonic acid to prostaglandins, is overexpressed in a variety of different tumors, including those of the colon, pancreas, lung, and head and neck. We used in situ hybridization with a digoxgenin-labeled COX-2 antisense riboprobe to assess the presence of strong or intermediate versus weak or absent COX-2 expression in specimens from 160 patients with stage I non-small cell lung cancer (NSCLC). Of these, 3 specimens had strong expression, 69 had intermediate expression of COX-2, 24 had weak expression, and 64 had no detectable COX-2. The strength of COX-2 expression was associated with a worse overall survival rate ( P = 0.001) and a worse disease-free survival rate ( P = 0.022). The median survival times for the strong, intermediate or weak, and null COX-2 expressors were 1.04, 5.50, and 8.54 years, respectively. Interestingly, all three specimens with strong COX-2 expression came from patients who died within 18 months. Retinoic acid receptor β (RAR-β) is a nuclear retinoid receptor whose expression is frequently lost in aerodigestive tract carcinogenesis. We previously demonstrated that expression of RAR-β in stage I NSCLC indicates a poor prognosis. Retinoids have been shown to prevent induction of COX-2 by mitogens and tumor promoters. Expression of COX-2 correlated with RAR-β expression ( P = 0.053), but not with k- ras mutational status, vascular endothelial growth factor, basic fibroblast growth factor, interleukin 8 levels, or other markers of angiogenesis, invasion, and metastases. Thus, like RAR-β positivity, COX-2 overexpression appears to portend a shorter survival among patients with early stage non-small cell lung cancer. Future studies of RAR-β and COX-2 regulation in NSCLC should further the development of prevention and therapy interventions with retinoids and/or COX-2 antagonists in this patient population.