Role of COX-2 in tumor progression and survival of head and neck squamous cell carcinoma

• Authors: Nabil F. Saba, Emory University; Misun Choi, Emory University; Susan Muller, Emory University; Hyung Ju C. Shin, Quest Diagnostics; Mourad Tighiouart, Emory University; Vassiliki A Papadimitrakopoulou, M.D. Anderson Cancer Center; Adel K El-Naggar, M.D. Anderson Cancer Center; Fadlo Khuri, Emory University; Georgia Chen, Emory University; Dong M Shin, Emory University
• Journal Title: Cancer Prevention Research
• Volume: Volume 2, Number 9
• Publisher: American Association for Cancer Research | 2009-09, Pages 823-829
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1158/1940-6207.CAPR-09-0077
• Subjects: Health Sciences, Oncology
• Keywords: COX-2; Head and neck cancer; premalignancy; chemoprevention; cyclooxygenase 2

Abstract

Inhibition of cyclooxygenase-2 (COX-2) pathways may have significant implications for the prevention and treatment of head and neck squamous cell carcinoma (HNSCC). COX-2 is overexpressed in both premalignant lesions and invasive HNSCC. We examined COX-2 expression by immunohistochemistry in normal tissues, different stages of premalignant lesions, and carcinoma in-situ (CIS). We also evaluated the correlation between COX-2 expression and clinical characteristics of HNSCC patients. Tissue specimens were obtained from: premalignant lesions from 25 subjects enrolled in a biochemoprevention trial; tumor samples collected at diagnosis from 38 HNSCC patients enrolled in an induction chemotherapy trial; and normal control tissues from 10 non-cancer, non-smoking subjects. COX-2 was expressed in early and intermediate stages of premalignant lesions, increasing first in the basal and parabasal layers, then lower spinous, and upper spinous layers. This correlation was noted in normal epithelium (p<0.0001), histologically normal in-field samples (p<0.0001), low-grade dysplasia (p=0.024), and moderate-grade dysplasia (p=0.009), but was lost in the majority of high-grade dysplasia/CIS (p=0.896). COX-2 expression was also noted to increase progressively through the early stages of premalignancy, and to decrease in severe/CIS stage and invasive carcinoma. COX-2 expression in tumors from patients treated with induction chemotherapy was correlated with overall survival after controlling for clinical variables. These findings elucidate the differential expression pattern of COX-2 in stages of head and neck premalignant lesions and invasive carcinoma, supporting the rationale for COX-2 inhibition as an important strategy for cancer chemoprevention. Further validation of COX-2 expression is needed in prospective ongoing chemoprevention trials.