Chemokine Receptor CXCR4 Expression Correlates with Tumor Grade in Pulmonary Neuroendocrine Carcinomas.
Sean Kirby, Nasser Mohd, Jin Jen, William Travis, Teri Franks, Charles Hitchcock, Weiqiang Zhao, Ramesh Ganju, Konstantin Shilo. The Ohio State University Medical Center, Columbus; Mayo Clinic, Rochester, MN; Memorial Sloan Kettering Cancer Center, New York, NY; AFIP, Washington, DC
Background: Chemokine receptor-4 (CXCR4) expression has been implicated in promoting metastasis in a variety of cancers including non-small cell lung carcinoma (NSCLC). However, there are conflicting results regarding the significance of its expression patterns (nuclear vs. cytoplasmic) and their relationship to outcome. Little is known about its expression in small cell lung carcinoma (SCLC), the lung carcinoma with the greatest metastatic potential. The aim of this study was to investigate CXCR4 expression in a wide range of pulmonary neuroendocrine carcinomas (NEC), including SCLC, and its possible association with clinical-pathological findings.
Design: Clinical-pathological features of 156 patients with NEC (73 men and 83 women, mean age of 59±15 years; range 19–83; median 62 years) were analyzed with regard to CXCR4 expression. Tissue microarray based samples were studied for CXCR4 (1:50, rabbit polyclonal, ab2074, Abcam, Cambridge, MA) expression by immunohistochemistry. The results were evaluated in comparison to normal lung parenchyma and recorded as negative, cytoplasmic, and nuclear. Correlation of the CXCR4 expression with clinical-pathological variables was performed utilizing statistical package JMP 8.0 (SAS Inc., Cary, NC).
Results: Cytoplasmic CXCR4 expression was detected in 53.8% (86/158) of pulmonary NEC: 26.3% of typical carcinoid (TC), 13.5% of atypical carcinoid (AC), 4.5% of large cell neuroendocrine carcinoma (LCNEC), and 10.9% of small cell lung carcinoma (SCLC). Nuclear CXCR4 expression was detected in 45.0% (72/158) of pulmonary NEC: 0.6% of TC, 4.5% of AC, 9.6% of LCNEC, and 28.9% of SCLC. Nuclear CXCR4 expression correlated with tumor grade (p<.05) but not with other clinical-pathological findings.
Conclusions: CXCR4 is observed in a significant percentage of pulmonary NEC. Nuclear CXCR4 expression correlates with grade of pulmonary NEC. The association between CXCR4 and SCLC suggests that aberrant nuclear CXCR4 expression may play role in metastasis as reported in NSCLC.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 249, Wednesday Morning