Prognostic value of immunoexpression of CCR4, CCR5, CCR7 and CXCR4 in squamous cell carcinoma of tongue and floor of the mouth.

LMR Paranaiba,WA Gonzalez-Arriagada,P Olivero,JBM Janini,C Lozano-Burgos,CB Domingueti

doi:10.4317/medoral.22904

LMR Paranaiba, WA Gonzalez-Arriagada + Show 4 more

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https://doi.org/10.4317/medoral.22904

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Abstract

BackgroundDiverse studies have evidenced that chemokines can play a critical role in pathogenesis of oral squamous cell carcinoma (SCC). The main chemokines involved in oral carcinogenesis, tumor invasion and metastasis are CCR4, CCR5, CCR7 and CXCR4, and our aim was to evaluate the prognostic value of the immunoexpression of these chemokines in SCC of tongue and floor of the mouth.Material and MethodsA retrospective descriptive study of the immunohistochemical expression of CCR4, CCR5, CCR7 and CXCR4 in paraffin-embedded samples of 124 patients with SCC of the tongue and floor of the mouth was performed, considering 98 cases from Brazil and 26 cases from Chile. Associations between variables were analyzed using chi-square test. Survival curves were performed using the Kaplan-Meier method and compared with long-rank test. For multivariate survival analysis, the Cox hazard model was established. The level of significance established was p≤0.05.ResultsThe statistical analysis showed that samples with well or moderate WHO model differentiation (p=0.001) and a high expression of CCR5 (p=0.05) were significantly associated with a higher disease specific survival, which were also observed in Cox´s multivariate analysis (p=0.01). A higher expression of CCR7 (p=0.01) interfered significantly in disease-free survival in univariate analysis and in Cox´s multivariate analysis (p=0.05).ConclusionsThese results support additional evidence, showing that chemokine receptors CCR5 and CCR7 are helpful as biomarkers of poor prognosis in patients with SCC of the tongue and floor of the mouth. Key words:Oral squamous cell carcinoma, prognosis, survival, chemokine receptor.

Highlights

Squamous cell carcinoma (SCC) is a malignant neoplasm, accounting for more than 90% of malignancies in the oral cavity [1]
These results support additional evidence, showing that chemokine receptors CCR5 and CCR7 are helpful as biomarkers of poor prognosis in patients with squamous cell carcinoma (SCC) of the tongue and floor of the mouth
Have been reported that CXCR4 mediate growing signals and promote metastasis [10], CCR5 acts in recruitment of effector cells and antigen-presenting cells [12], CCR4 and CCR7 has been associated to the ability of neoplastic cells to promote lymph node metastasis

Summary

Conclusions

Our results show that CCR7 and CCR5 can be helpful as prognostic markers and as a therapeutic approach of patients with SCC of tongue and floor of the mouth. The association of CCR5 and CCR7 chemokine/ chemokine receptor axis with poor prognosis in oral SCC needs future molecular research to study mechanisms that lead to tumor growth and progression, considering that immunohistochemical studies can only confirm statistical relationship. We suggest the name oncochemotaxis for the mechanism that lead the malignant cells to invasion and migration to the lymph node through the expression of chemokine receptors in its surface attracted by chemokines

Introduction

Results