title: Evaluation of cannabinoid CB1 and CB2 receptors expression in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients' survival.
abstract: Cannabinoid receptors (CB1R and CB2R) constitute essential members of the endocannabinoid system (ECS) which participates in many different functions indispensable to homeostatic regulation in several tissues, exerting also antitumorigenic effects. The present study aimed to assess the clinical significance of CB1R and CB2R protein expression in mobile tongue squamous cell carcinoma (SCC). CB1R and CB2R expression was assessed immunohistochemically on 28 mobile tongue SCC tissue samples and was analyzed in relation with clinicopathological characteristics and overall and disease-free patients' survival. CB1R, CB2R, and concomitant CB1R/CB2R expression was significantly increased in older compared to younger mobile tongue SCC patients (p = 0.0243, p = 0.0079, and p = 0.0366, respectively). Enhanced CB2R and concomitant CB1R/CB2R expression was significantly more frequently observed in female compared to male mobile tongue SCC patients (p = 0.0025 and p = 0.0016, respectively). Elevated CB2R expression was significantly more frequently observed in mobile tongue SCC patients presenting well-defined tumor shape compared to those with diffuse (p = 0.0430). Mobile tongue SCC patients presenting enhanced CB1R, CB2R, or concomitant CB1R/CB2R expression showed significantly longer overall (log-rank test, p = 0.004, p = 0.011, p = 0.018, respectively) and disease-free (log-rank test, p = 0.003, p = 0.007, p = 0.027, respectively) survival times compared to those with low expression. In multivariate analysis, CB1R was identified as an independent prognostic factor for disease-free patients' survival (Cox-regression analysis, p = 0.032). The present study provides evidence that CB1R and CB2R may play a role in the pathophysiological aspects of the mobile tongue SCC and even each molecule may constitute a potential target for the development of novel anti-cancer drugs for this type of malignancy.
authors.affiliation: First Department of Pathology, Medical School, University of Athens, 75 M. Asias str., Goudi, Athens, Greece, GR11527. statheocharis@yahoo.com.|Department of Pathology, Institut Curie, Paris, France. statheocharis@yahoo.com.
authors.forename: Stamatios
authors.initials: S
authors.lastname: Theocharis
authors.affiliation: First Department of Pathology, Medical School, University of Athens, 75 M. Asias str., Goudi, Athens, Greece, GR11527.|Department of Food Science and Nutrition, University of the Aegean, Lemnos, Greece.
authors.forename: Constantinos
authors.initials: C
authors.lastname: Giaginis
authors.affiliation: First Department of Pathology, Medical School, University of Athens, 75 M. Asias str., Goudi, Athens, Greece, GR11527.
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Alexandrou
authors.affiliation: Department of Head and Neck Surgery, Institut Curie, Paris, France.
authors.forename: Jose
authors.initials: J
authors.lastname: Rodriguez
authors.affiliation: First Department of Pathology, Medical School, University of Athens, 75 M. Asias str., Goudi, Athens, Greece, GR11527.
authors.forename: Jason
authors.initials: J
authors.lastname: Tasoulas
authors.affiliation: First Department of Pathology, Medical School, University of Athens, 75 M. Asias str., Goudi, Athens, Greece, GR11527.
authors.forename: Eugene
authors.initials: E
authors.lastname: Danas
authors.affiliation: First Department of Pathology, Medical School, University of Athens, 75 M. Asias str., Goudi, Athens, Greece, GR11527.
authors.forename: Efstratios
authors.initials: E
authors.lastname: Patsouris
authors.affiliation: Department of Pathology, Institut Curie, Paris, France.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Klijanienko
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D011379:Prognosis; D016016:Proportional Hazards Models; D043884:Receptor, Cannabinoid, CB1 / Q000096:biosynthesis*; D043885:Receptor, Cannabinoid, CB2 / Q000096:biosynthesis*; D012737:Sex Factors; D014062:Tongue Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery
chemical_list: D014408:Biomarkers, Tumor; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2
keywords: Cannabinoid receptors; Clinicopathological parameters; Immunohistochemistry; Mobile tongue squamous cell carcinoma; Prognosis