title: Tumour epithelial expression levels of endocannabinoid markers modulate the value of endoglin-positive vascular density as a prognostic marker in prostate cancer.
abstract: Fatty acid amide hydrolase (FAAH) is responsible for the hydrolysis of the endogenous cannabinoid (CB) receptor ligand anandamide. Here we have investigated whether the expression levels of FAAH and CB1 receptors influence the prognostic value of markers of angiogenesis in prostate cancer. Data from a cohort of 419 patients who were diagnosed with prostate cancer at transurethral resection for lower urinary tract symptoms, of whom approximately 2/3 had been followed by expectancy, were used. Scores for the angiogenesis markers endoglin and von Willebrand factor (vWf), the endocannabinoid markers fatty acid amide hydrolase (FAAH) and cannabinoid CB1 receptors and the cell proliferation marker Ki-67 were available in the database. For the cases followed by expectancy, the prognostic value of endoglin was dependent upon the tumour epithelial FAAH immunoreactivity (FAAH-IR) and CB1IR scores, and the non-malignant epithelial FAAH-IR scores, but not the non-malignant CB1IR scores or the tumour blood vessel FAAH-IR scores. This dependency upon the tumour epithelial FAAH-IR or CB1IR scores was less apparent for vWf, and was not seen for Ki-67. Using an endoglin cut-off value of 10 positively stained vessels per core and a median split of tumour FAAH-IR, four groups could be generated, with 15year of disease-specific survival (%) of 68±7 (low endoglin, low FAAH), 45±11 (high endoglin, low FAAH), 77±6 (low endoglin, high FAAH) and 21±10 (high endoglin, high FAAH). Thus, the cases with high endoglin and high FAAH scores have the poorest rate of disease-specific survival. At diagnosis, the number of cases with tumour stages 1a-1b relative to stages 2-4 was sensitive to the endoglin score in a manner dependent upon the tumour FAAH-IR. It is concluded that the prognostic value of endoglin as a marker of neovascularisation in prostate cancer can be influenced by the expression level of markers of the endocannabinoid system. This article is part of a Special Issue entitled Lipid Metabolism in Cancer.
authors.affiliation: Pharmacology Unit, Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden. Electronic address: cf@pharm.umu.se.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Fowler
authors.forename: Andreas
authors.initials: A
authors.lastname: Josefsson
authors.forename: Lina
authors.initials: L
authors.lastname: Thors
authors.forename: Sui Chu
authors.initials: SC
authors.lastname: Chung
authors.forename: Peter
authors.initials: P
authors.lastname: Hammarsten
authors.forename: Pernilla
authors.initials: P
authors.lastname: Wikström
authors.forename: Anders
authors.initials: A
authors.lastname: Bergh
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D063388:Endocannabinoids / Q000378:metabolism*; D000071063:Endoglin; D006801:Humans; D008297:Male; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011956:Receptors, Cell Surface / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C064206:ENG protein, human; D063388:Endocannabinoids; D000071063:Endoglin; D011956:Receptors, Cell Surface