A high cannabinoid CB₁ receptor immunoreactivity is associated with disease severity and outcome in prostate cancer

Abstract 

In the light of findings indicating that cannabinoids can affect the proliferation of a number of cancer cell types and that cannabinoid receptor expression is higher in prostate cancer cell lines than in non-malignant cells, we investigated whether the level of cannabinoid 1 receptor immunoreactivity (CB₁IR) in prostate cancer tissues is associated with disease severity and outcome. Formalin-fixed paraffin-embedded non-malignant and tumour tissue samples from patients who were diagnosed with prostate cancer at a transurethral resection for voiding problems were used. CB₁IR, which was scored in a total of 399 cases, was associated with the epithelial cell membranes, with little staining in the stroma. Patients with a tumour CB₁IR score greater or equal to the median (2) had a significantly higher proportion of Gleason scores 8–10, metastases at diagnosis, tumour size and rate of cell proliferation at diagnosis than patients with a score<2. For 269 cases, tumour CB₁IR was measured for patients who only received palliative therapy at the end stages of the disease, allowing the influence of CB₁IR upon the disease outcome to be determined. Receiver operating characteristic (ROC) curves showed an area under the curve of 0.67 (95% confidence limits 0.59–0.74) for CB₁IR in the tumour. CB₁IR in non-malignant tissue was not associated with disease outcome. A tumour CB₁IR score⩾2 was associated with a significantly lower disease specific survival. A Cox proportional hazards regression indicated that the tumour CB₁IR score and the Gleason score were independent prognostic variables. It is concluded that a high tumour CB₁IR score is associated with prostate cancer severity and outcome.

Keywords: Prostate cancer, Cannabinoid receptor, Gleason score, Kaplan–Meier analysis