Introduction: Papillary thyroid carcinoma is the most common malignancy of the endocrine system. Most papillary thyroid carcinoma patients enjoy excellent outcomes. However, in patients with biologically aggressive features, additional prognostic and predictive data may aid disease management. Dysregulation of the endocannabinoid system including the cannabinoid recep- tors 1 and 2 (CB-1R and CB-2R) during carcinogenesis has been extensively studied over the last few decades. The aim of this study was to evaluate immunohistochemically the expression levels of both receptors in patients with papillary thyroid carcin- oma and benign diseases, and to compare these rates and the histopathologically and clinically prognostic features.

Methods: The pathological materials and clinical data of 100 patients with papillary thyroid carcinoma and 40 with benign dis- eases were retrospectively re-evaluated. All tissues were immunohistochemically stained for CB-1R and CB-2R. The expression levels of CB-1R and CB-2R in papillary thyroid carcinomas, and benign lesions were recorded and compared with the patho- logical and clinical features.

Results: The expression levels of both receptors were significantly higher in papillary thyroid carcinoma patients than in those with benign conditions (P = 0.001). CB-1R expression correlated with both extrathyroidal extension (P = 0.022) and capsular invasion (P = 0.001). CB-2R expression was associated with the risk group of the American Thyroid Association stratification system (P = 0.004).

Conclusion: Our study suggests that increased cannabinoid receptor expression contributes to thyroid carcinogenesis. The CB-2R expression level could provide additional information aiding risk management. Furthermore, the CB-1R and CB-2R anti- bodies might increase the accuracy of papillary thyroid carcinoma diagnosis when combined with the papillary thyroid carcinoma biomarkers assayed after fine-needle aspiration of neoplastic cells.