Coordinated Upregulation of COX-2 and NF-κB Is a Steady Feature of Laryngeal Carcinogenesis

Abstract

Background/Aims: Laryngeal cancer is the endpoint of a multistage process involving hyperplastic and dysplastic lesions, not adequately defined in their molecular aspect. Our objective was to evaluate the expression of the prostaglandin-synthesizing enzyme cyclooxygenase-2 (COX-2) and the chief transcription factor nuclear factor-ĸB (NF-ĸB) in laryngeal carcinomas and their precursors, as well as to explore any association between the two molecules. Methods: We performed paraffin section immunohistochemistry for COX-2 and the p65 subunit of NF-ĸB, in tissues from 129 patients with tumors or premalignancies. p65 cytoplasmic and nuclear immunostaining were listed individually. Results: COX-2 was positively correlated with histopathological grading from normal mucosa to carcinomas (Spearman’s coefficient r_s = 0.286, p < 0.001). No association was revealed between COX-2 expression and tumor grade. p65 immunoreactivity, both of cytoplasmic and nuclear origin, increased along the carcinogenesis course, manifesting highest expression in invasive cancer (r_s = 0.419, p < 0.001 and r_s = 0.241, p < 0.001, respectively). Again, tumor grade had no influence on expression. COX-2 and p65 cytoplasmic, but no nuclear, expression showed a positive correlation (r_s = 0.352, p < 0.001). Conclusions: This study demonstrates that lesional advance in the larynx towards cancer is marked by ongoing upregulation of COX-2 and NF-ĸB. Synchronism between individual expressions may denote a regulatory role of the latter in COX-2 transactivation.