Clinical Significance of Cannabinoid Receptors CB1 and CB2 Expression in Human Malignant and Benign Thyroid Lesions

The endocannabinoid system is comprised of cannabinoid receptors (CB1 and CB2), their endogenous ligands (endocannabinoids), and proteins responsible for their metabolism participate in many different functions indispensable to homeostatic regulation in several tissues, exerting also antitumorigenic effects. The present study aimed to evaluate the clinical significance of CB1 and CB2 expression in human benign and malignant thyroid lesions. CB1 and CB2 proteins' expression was assessed immunohistochemically on paraffin-embedded thyroid tissues obtained from 87 patients with benign (n = 43) and malignant (n = 44) lesions and was statistically analyzed with clinicopathological parameters, follicular cells' proliferative capacity, and risk of recurrence rate estimated according to the American Thyroid Association (ATA) staging system. Enhanced CB1 and CB2 expression was significantly more frequently observed in malignant compared to benign thyroid lesions (p = 0.0010 and p = 0.0005, resp.). Enhanced CB1 and CB2 expression was also significantly more frequently observed in papillary carcinomas compared to hyperplastic nodules (p = 0.0097 and p = 0.0110, resp.). In malignant thyroid lesions, elevated CB2 expression was significantly associated with the presence of lymph node metastases (p = 0.0301). Enhanced CB2 expression was also more frequently observed in malignant thyroid cases with presence of capsular (p = 0.1165), lymphatic (p = 0.1989), and vascular invasion (p = 0.0555), as well as in those with increased risk of recurrence rate (p = 0.1165), at a nonsignificant level though, whereas CB1 expression was not associated with any of the clinicopathological parameters examined. Our data suggest that CB receptors may be involved in malignant thyroid transformation and especially CB2 receptor could serve as useful biomarker and potential therapeutic target in thyroid neoplasia.