Abstract
The cannabinoid system has been considered to be a potential target of colorectal carcinoma therapy. The aim of this study was to address the correlation between cannabinoid type 1 (CB1) receptor expression and disease severity/outcomes in patients with colorectal cancer (CRC). CB1 receptor expression was analyzed by immunohistochemistry using tissue microarrays in consecutive patients who underwent surgical resection (n=534). CB1 receptor expression was categorized as a high (≥66%) vs. low (<66%) immunopercentage as a median split, and was analyzed in relation to disease severity and overall survival. CB1 receptor expression was observed in 409 patients (76.6%). Low CB1 receptor expression was more frequently identified in stage IV than in stage I/II or III cancer (P<0.01 for both). In stage IV CRC, high vs. low CB1 expression was correlated with a statistically significant poorer overall survival (P=0.033) that was independent of age, R0 resection, tumor differentiation and chemotherapy [hazard ratio (HR), 1.805; 95% confidence interval (CI), 1.042-3.094; P=0.035]. However, CB1 expression was not observed to be correlated with patient survival following surgery in stage I/II or III cancer. The high immunoreactivity of the cannabinoid type 1 receptor is a significant prognostic factor following surgery in stage IV CRC.