Low COX2 in tumor and upregulation in stroma mark laryngeal squamous cell carcinoma progression.

Abstract

Invasive squamous cell carcinomas (SCC) of the larynx, like most solid tumors, are surrounded by a reactive stroma, in which cancer associated fibroblasts (CAFs) are the predominant cell type. This mesenchymal reaction may affect cancer progression multiply. The proinflammatory enzyme cyclooxygenase-2 (COX-2) has been correlated with head and neck cancer. This study aims to explore the impact of epithelial and stromal COX-2 expression on SCC behavior. Retrospective case review study performed in a tertiary health center institution. Double immunohistochemistry of COX-2 and the CAF marker alpha-smooth muscle actin (alpha-SMA) was utilized in 97 laryngeal cancer patients. Follow-up data were collected in 52 cases. Low COX-2 immunostaining in cancer cells was associated with advanced grade (P = .044) and shorter recurrence-free period (P = .035). CAF expression was positively correlated with the grade of the infiltrating tumor (P = .030). In laryngeal SCCs, COX-2 may exert its deleterious effect by alterations in the tumor microenvironment. CAF-derived, COX-2-mediated paracrine influences on malignant cells possibly facilitate cancer progression. Overlooking the stromal remodeling could account for unsuccessful treatments of epithelial neoplasms.