CXCR4 and CXCL12 immunoreactivities differentiate primary non-small-cell lung cancer with or without brain metastases

Article type: Research Article

Authors: Paratore, Sabrina^{a; b} | Banna, Giuseppe Luigi^c | D'Arrigo, Maria^b | Saita, Salvatore^b | Iemmolo, Rosario^b | Lucenti, Letizia^b | Bellia, Domenico^{a; b} | Lipari, Helga^b | Buscarino, Calogero^b | Cunsolo, Rosario^b | Cavallaro, Sebastiano^{a; b; *}

Affiliations: [a] Functional Genomics Center, Institute of Neurological Sciences, Italian National Research Council, Catania, Italy | [b] Policlinico-Vittorio Emanuele, University Hospital, Catania, Italy | [c] Division of Medical Oncology, Cannizzaro Hospital, Catania, Italy

Correspondence: [*] Corresponding author: Sebastiano Cavallaro, M.D., Ph.D., Istituto di Scienze Neurologiche, CNR, Via Paolo Gaifami, 18, 95125 Catania, Italy. Tel.: +39 095 7436634; Fax: +39 095 7122426; E-mail: s.cavallaro@isn.cnr.it.

Abstract: Synchronous or metachronous brain metastases (BMs) occur in about 33% of patients affected by non-small-cell lung cancer (NSCLC). To date, no reliable biological marker is able to identify patients who will develop BMs. In the present study, using a quantitative double-labeling immunofluorescence analysis, we evaluated the expression of chemokine CXCL12 and its receptor, CXCR4, in primary NSCLC histological specimens of patients with and without BMs. The immunoreactivity of CXCL12 and CXCR4 was significantly higher in NSCLC samples of patients with BMs. We performed Receiver Operating Characteristics (ROC) analysis in order to define optimal cut-off values for CXCL12 and CXCR4 immunoreactivity that could discriminate between NSCLC patients without and with BMs. ROC curves showed a good diagnostic accuracy and adequate predictive power for both CXCL12 and CXCR4. These findings suggest a possible role for the CXCL12/CXCR4 axis in the metastatic evolution of NSCLC, and its potential use as prognostic markers and drug targets.

Keywords: Brain metastases, chemokines, CXCL12, CXCR4, immunohistochemistry, lung cancer, marker, metastasis, prognosis

DOI: 10.3233/CBM-2011-0232

Journal: Cancer Biomarkers, vol. 10, no. 2, pp. 79-89, 2012