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Focal Adhesion Kinase Expression in Human Neuroblastoma: Immunohistochemical and Real-time PCR Analyses

Authors' Affiliations: Departments of ¹ Surgery and ² Pathology, University of Florida; ³ Epidemiology and Health Policy Research, Children's Oncology Group, Gainesville, Florida

Requests for reprints: Elizabeth A. Beierle, Department of Surgery, University of Florida, College of Medicine, P.O. Box 100286, J. Hillis Miller Health Science Center, Gainesville, FL 32610-0286. Phone: 352-392-3718; Fax: 352-392-9081; E-mail: beierea{at}surgery.ufl.edu.

Purpose: The focal adhesion kinase (FAK) is a nonreceptor protein tyrosine kinase important in signaling between cells and their extracellular matrix. Studies have shown that FAK expression is up-regulated in several human tumors and is related to tumor progression. We recently found an increase in p125^FAK expression in human neuroblastoma cells lines and wished to determine its expression in human neuroblastoma specimens and evaluate for a possible correlation between p125^FAK expression and known prognostic factors for neuroblastoma. We hypothesized that p125^FAK expression would be up-regulated in advanced human neuroblastomas.

Experimental Design: Using immunohistochemical techniques with monoclonal antibody 4.47 specific for p125^FAK expression, we analyzed 70 formalin-fixed, paraffin-embedded human neuroblastoma specimens for p125^FAK staining. In addition, real-time PCR was used to determine the abundance of FAK mRNA in 17 matched human neuroblastoma mRNA specimens.

Results: FAK staining was present in 51 of the 70 tumor specimens (73%). Immunohistochemical staining of p125^FAK in the ganglion-type tumor cells correlated with advanced International Neuroblastoma Staging System tumor stages and FAK mRNA abundance. In addition, p125^FAK staining was significantly increased in stage IV tumors with amplification of the N-MYC oncogene.

Conclusions: These novel findings provide evidence that FAK is expressed by advanced-stage neuroblastoma and provide a rationale for targeting FAK in the treatment of this tumor.