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

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. (c) 2008 Elsevier Ltd. All rights reserved.