Clinicopathological significance of chemokine receptor (CCR1, CCR3, CCR4, CCR5, CCR7 and CXCR4) expression in head and neck squamous cell carcinomas

J Oral Pathol Med. 2018 Sep;47(8):755-763. doi: 10.1111/jop.12736. Epub 2018 Jun 8.

Abstract

Background: Head and neck squamous cell carcinoma shows high prevalence of lymph node metastasis at diagnosis, and despite the advances in treatment, the overall 5-year survival is still under 50%. Chemokine receptors have a role in the development and progression of cancer, but their effect in head and neck carcinoma remains poorly characterised. This study aimed to assess the prognostic value of CCR1, CCR3, CCR4, CCR5, CCR7 and CXCR4 in head and neck squamous cell carcinomas.

Methods: Immunohistochemical expression of chemokine receptors was evaluated in a retrospective cohort of 76 cases of head and neck squamous cell carcinoma. Clinicopathological associations were analysed using the chi-square test, survival curves were analysed according to the Kaplan-Meier method, and the Cox proportional hazard model was applied for multivariate survival analysis.

Results: The chemokine receptors were highly expressed in primary carcinomas, except for CCR1 and CCR3. Significant associations were detected, including the associations between CCR5 expression and lymph node metastasis (N stage, P = .03), advanced clinical stage (P = .003), poor differentiation of tumours (P = .05) and recurrence (P = .01). The high expression of CCR5 was also associated with shortened disease-free survival (HR: 2.85, 95% CI: 1.09-8.14, P = .05), but the association did not withstand the Cox multivariate survival analysis. At univariate analysis, high expression of CCR7 was associated with disease-free survival and low levels of CXCR4 were significantly associated with both disease-specific and disease-free survival.

Conclusions: These findings show that chemokine receptors may have an important role in head and neck squamous cell carcinoma progression, regional lymph node metastasis and recurrence.

Keywords: G-protein-coupled receptors; chemokine receptor; head and neck cancer; lymph node; lymphatic metastasis; membrane proteins.

MeSH terms

  • Aged
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Gene Expression*
  • Head and Neck Neoplasms / diagnosis*
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / pathology*
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Prognosis
  • Receptors, CCR1 / genetics
  • Receptors, CCR1 / metabolism
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / metabolism
  • Receptors, Chemokine / genetics*
  • Receptors, Chemokine / metabolism*
  • Squamous Cell Carcinoma of Head and Neck / diagnosis*
  • Squamous Cell Carcinoma of Head and Neck / mortality
  • Squamous Cell Carcinoma of Head and Neck / pathology*
  • Survival Analysis

Substances

  • CXCR4 protein, human
  • Receptors, CCR1
  • Receptors, CXCR4
  • Receptors, Chemokine