Theocharis Stamatios, Giaginis Constantinos, Alexandrou Paraskevi, Rodriguez Jose, Tasoulas Jason, Danas Eugene, Patsouris Efstratios, Klijanienko Jerzy
First Department of Pathology, Medical School, University of Athens, 75 M. Asias str., Goudi, Athens, Greece, GR11527.
Department of Pathology, Institut Curie, Paris, France.
Tumour Biol. 2016 Mar;37(3):3647-56. doi: 10.1007/s13277-015-4182-8. Epub 2015 Oct 12.
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.
大麻素受体（CB1R和CB2R）是内源性大麻素系统（ECS）的重要成员，该系统参与多种组织中稳态调节所必需的许多不同功能，还具有抗肿瘤作用。本研究旨在评估CB1R和CB2R蛋白表达在移动性舌鳞状细胞癌（SCC）中的临床意义。采用免疫组织化学方法对28例移动性舌SCC组织样本中的CB1R和CB2R表达进行评估，并分析其与临床病理特征以及患者总生存期和无病生存期的关系。与年轻的移动性舌SCC患者相比，老年患者的CB1R、CB2R及CB1R/CB2R伴随表达显著增加（分别为p = 0.0243、p = 0.0079和p = 0.0366）。与男性移动性舌SCC患者相比，女性患者中CB2R及CB1R/CB2R伴随表达增强更为常见（分别为p = 0.0025和p = 0.0016）。与肿瘤形态弥漫的患者相比，肿瘤形态边界清晰的移动性舌SCC患者中CB2R表达升高更为常见（p = 0.0430）。CB1R、CB2R或CB1R/CB2R表达增强的移动性舌SCC患者的总生存期（对数秩检验，分别为p = 0.004、p = 0.011、p = 0.018）和无病生存期（对数秩检验，分别为p = 0.003、p = 0.007、p = 0.027）显著长于表达低的患者。在多因素分析中，CB1R被确定为无病患者生存期的独立预后因素（Cox回归分析，p = 0.032）。本研究提供了证据表明CB1R和CB2R可能在移动性舌SCC的病理生理过程中发挥作用，甚至每个分子都可能成为开发针对这种恶性肿瘤的新型抗癌药物的潜在靶点。
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