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Evaluation of cannabinoid CB1 and CB2 receptors expression in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients’ survival

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Tumor Biology

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.

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Acknowledgments

We would like to thank Ms Dimitra Lambiri and Ms Eugenie Ventouri for their excellent technical assistant. All authors verify that they have not accepted any funding or support from an organization that may in any way gain or lose financially from the results of the present study. All authors verify that they have not been employed by an organization that may in any way gain or lose financially from the results of the present study.

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Authors and Affiliations

  1. First Department of Pathology, Medical School, University of Athens, 75 M. Asias str., Goudi, Athens, Greece, GR11527

    Stamatios Theocharis, Constantinos Giaginis, Paraskevi Alexandrou, Jason Tasoulas, Eugene Danas & Efstratios Patsouris

  2. Department of Pathology, Institut Curie, Paris, France

    Stamatios Theocharis & Jerzy Klijanienko

  3. Department of Food Science and Nutrition, University of the Aegean, Lemnos, Greece

    Constantinos Giaginis

  4. Department of Head and Neck Surgery, Institut Curie, Paris, France

    Jose Rodriguez

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  1. Stamatios Theocharis
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  2. Constantinos Giaginis
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  3. Paraskevi Alexandrou
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  4. Jose Rodriguez
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  8. Jerzy Klijanienko
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Correspondence to Stamatios Theocharis.

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Theocharis, S., Giaginis, C., Alexandrou, P. et al. Evaluation of cannabinoid CB1 and CB2 receptors expression in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients’ survival. Tumor Biol. 37, 3647–3656 (2016). https://doi.org/10.1007/s13277-015-4182-8

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  • DOI: https://doi.org/10.1007/s13277-015-4182-8

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