title: CXCL12, CXCR4 and CXCR7 expression in brain metastases.
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.
authors.affiliation: Department of Neurology, Fondazione IRCCS Istituto Neurologico C. Besta, Via Celoria 11, Milan, Italy. salmaggi@istituto-besta.it
authors.forename: Andrea
authors.initials: A
authors.lastname: Salmaggi
authors.forename: Emanuela
authors.initials: E
authors.lastname: Maderna
authors.forename: Chiara
authors.initials: C
authors.lastname: Calatozzolo
authors.forename: Paola
authors.initials: P
authors.lastname: Gaviani
authors.forename: Alessandra
authors.initials: A
authors.lastname: Canazza
authors.forename: Ida
authors.initials: I
authors.lastname: Milanesi
authors.forename: Antonio
authors.initials: A
authors.lastname: Silvani
authors.forename: Francesco
authors.initials: F
authors.lastname: DiMeco
authors.forename: Antonino
authors.initials: A
authors.lastname: Carbone
authors.forename: Bianca
authors.initials: B
authors.lastname: Pollo
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism* / Q000556:secondary*; D054377:Chemokine CXCL12 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4