Brain metastases occur in about 25% of patients who die of cancer. The most common sources of brain metastases in adults are lung, breast, kidney, colorectal cancer and melanoma. The chemokine/receptor system CXCL12/CXCR4 plays a key role in multiple biological functions; among these, homing of neoplastic cells from the primary site to the target and metastasis progression. Recently, an alternative CXCL12 receptor CXCR7 has been discovered. The aim of our study was to investigate the expression of CXCL12 and its receptors CXCR4 and CXCR7 by immunohistochemistry in 56 patients with metastatic brain disease from different non-CNS primary tumors and evaluate their prognostic relevance as well as that of other patient/treatment-related features on patient survival. CXCL12 showed an expression in tumor cells and in tumor vessels; CXCR7 was expressed by tumor and endothelial cells (both within the tumor and in the adjacent brain tissue), while CXCR4 showed a positivity in all samples with a nuclear pattern. Among the investigated immunohistochemical parameters, only CXCL12 expression in tumor endothelial cells showed a statistically significant correlation with shorter survival (p = 0.04 log-rank), perhaps identifying more aggressive tumors. Thus, this is the first study evaluating at the same time the expression of CXCL12 and its two receptors in a cohort of brain metastases.

CXCL12, CXCR4 and CXCR7 expression in brain metastases / A. Salmaggi, E. Maderna, C. Calatozzolo, P. Gaviani, A. Canazza, I. Milanesi, A. Silvani, F. Di Meco, A. Carbone, B. Pollo. - In: CANCER BIOLOGY & THERAPY. - ISSN 1555-8576. - 8:17(2009 Sep), pp. 1608-1614.

CXCL12, CXCR4 and CXCR7 expression in brain metastases

A. Canazza;I. Milanesi;A. Silvani;F. Di Meco;
2009

Abstract

Brain metastases occur in about 25% of patients who die of cancer. The most common sources of brain metastases in adults are lung, breast, kidney, colorectal cancer and melanoma. The chemokine/receptor system CXCL12/CXCR4 plays a key role in multiple biological functions; among these, homing of neoplastic cells from the primary site to the target and metastasis progression. Recently, an alternative CXCL12 receptor CXCR7 has been discovered. The aim of our study was to investigate the expression of CXCL12 and its receptors CXCR4 and CXCR7 by immunohistochemistry in 56 patients with metastatic brain disease from different non-CNS primary tumors and evaluate their prognostic relevance as well as that of other patient/treatment-related features on patient survival. CXCL12 showed an expression in tumor cells and in tumor vessels; CXCR7 was expressed by tumor and endothelial cells (both within the tumor and in the adjacent brain tissue), while CXCR4 showed a positivity in all samples with a nuclear pattern. Among the investigated immunohistochemical parameters, only CXCL12 expression in tumor endothelial cells showed a statistically significant correlation with shorter survival (p = 0.04 log-rank), perhaps identifying more aggressive tumors. Thus, this is the first study evaluating at the same time the expression of CXCL12 and its two receptors in a cohort of brain metastases.
adult; aged; biomarkers, tumor; brain neoplasms; chemokine CXCL12; cohort studies; disease progression; female; humans; immunohistochemistry; Kaplan-Meier estimate; male; middle aged; prognosis; receptors, CXCR4; survival rate
Settore MED/27 - Neurochirurgia
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/585371
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