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Overexpression of Focal Adhesion Kinase in Head and Neck Squamous Cell Carcinoma Is Independent of fak Gene Copy Number

Authors' Affiliations: ¹ Servicio de Otorrinolaringología y, ² Anatomía Patológica del Hospital Universitario Central de Asturias, and ³ Instituto Universitario de Oncologia del Principado de Asturias, Universidad de Oviedo, Spain

Requests for reprints: María Dolores Chiara, Departamento de Cirugía y Especialidades, Facultad de Medicina, 6^a planta, C/Julian Clavería s/n, E-33006-Oviedo, Asturias, Spain. Phone: 34-985-103589; Fax: 34-985-104198; E-mail: mdchiara.uo{at}uniovi.es.

The development of human malignancies can involve the aberrant regulation of intracellular signal transduction pathways that regulate cell-extracellular matrix interactions.

Purpose: In the current study, we aimed to evaluate focal adhesion kinase (FAK) at both genetic and protein expression levels in head and neck squamous cell carcinomas (HNSCC) and to explore the prognostic significance of FAK.

Experimental Design: A total of 211 tissue specimens, including 147 primary tumors, 56 lymph node metastases, 3 benign hyperplasias, and 5 dysplasias, were analyzed using immunohistochemistry. The fak gene dosage was determined in 33 tumors. Correlations among DNA, protein, and clinicopathologic variables were analyzed.

Results: FAK protein was overexpressed in HNSCCs compared with corresponding normal mucosa. High expression levels were found in 62% of the samples. Positive immunostaining was also detected in benign hyperplasias and preinvasive dysplastic lesions. All lymph node metastases examined showed FAK overexpression, with significant correlation with the expression in matched primary tumor. DNA copy number ratios for fak were higher in 39% of the tumors compared with normal mucosa. However, elevated FAK expression did not correlate with gains on DNA level, and not all cases with an amplification of the fak gene displayed protein overexpression. Similar data were obtained in five HNSCC-derived cell lines, in which FAK mRNA levels were precisely correlated with FAK protein levels. FAK protein overexpression in tumors correlated with nodal metastases.

Conclusions: These findings suggest an involvement of FAK in the onset and progression of HNSCC and provide an insight into a mechanism of FAK activation alternative to gene amplification.

Commentary

The Signaling and Biological Implications of FAK Overexpression in Cancer

Priscila M.F. Siesser and Steven K. Hanks
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