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Background  Recent data have indicated that there may be a dysregulation of endocannabinoid metabolism in cancer. Here we have investigated the expression of the endocannabinoid metabolising enzyme fatty acid amide hydrolase (FAAH) in a well characterised tissue microarray from patients diagnosed with prostate cancer at transurethral resection for voiding problems.    Methodology/Principal Findings  FAAH immunoreactivity (FAAH-IR) was assessed in formalin-fixed paraffin-embedded non-malignant and tumour cores from 412 patients with prostate cancer. CB 1  receptor immunoreactivity (CB 1 IR) scores were available for this dataset. FAAH-IR was seen in epithelial cells and blood vessel walls but not in the stroma. Tumour epithelial FAAH-IR was positively correlated with the disease severity at diagnosis (Gleason score, tumour stage, % of the specimen that contained tumour) for cases with mid-range CB 1 IR scores, but not for those with high CB 1 IR scores. For the 281 cases who only received palliative therapy at the end stages of the disease, a high tumour epithelial FAAH-IR was associated with a poor disease-specific survival. Multivariate Cox proportional-hazards regression analyses indicated that FAAH-IR gave additional prognostic information to that provided by CB 1 IR when a midrange, but not a high CB 1 IR cutoff value was used. Interleukin-4 (IL-4) receptor IR was found on tumour epithelial cells and incubation of prostate cancer PC-3 and R3327 AT1 cells with IL-4 increased their FAAH activity.    Conclusions/Significance  Tumour epithelial FAAH-IR is associated with prostate cancer severity and outcome at mid-range, but not high, CB 1 IR scores. The correlation with CB 1 IR in the tumour tissue may be related to a common local dysregulation by a component of the tumour microenvironment.

Fatty Acid Amide Hydrolase in Prostate Cancer: Association with Disease Severity and Outcome, CB1 Receptor Expression and Regulation by IL-4