CXCR4-CXCL12 axis and distant metastatic outgrowth in head and neck malignancy

Abstract

Background: To analyze whether distant metastatic outgrowth in different head and neck malignancies (HNM) underlies the CXCR4-CXCL12 axis as overriding molecular mechanism. Methods: Clinic-pathological data of 1,250 HNM was included. HNM were collected due to different capability to exhibit distant metastasis comprising basal cell, squamous cell, and adenoid-cystic carcinoma as well as melanoma. MMP2/9, TIMP1/2, CXCR4, and CXCL12 immunohistochemistry was done in 190 randomly selected specimens.Results: Immunohistochemistry visualized a significant increase in MMP2/9, TIMP1/2, CXCR4, and CXCL12 protein expression following the clinical occurrence of distant metastasis. CXCR4, CXCL12, and TIMP2-expression significantly increases with number of affected organs by distant metastasis. Cox regression demonstrated CXCR4-overexpression and advanced T-status being independent risk factors of distant metastasis associated death.Conclusion: The CXCR4-CXCL12 axis is associated with the occurrence of distant metastases in different HNM. The increased risk of distant metastasis associated death was identified at primary tumour site and, therefore, potentially influences further treatment protocols.