title: Overexpression of focal adhesion kinase in head and neck squamous cell carcinoma is independent of fak gene copy number.
abstract: The development of human malignancies can involve the aberrant regulation of intracellular signal transduction pathways that regulate cell-extracellular matrix interactions.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Servicio de Otorrinolaringología, Hospital Universitario Central de Asturias, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Canel
authors.forename: Pablo
authors.initials: P
authors.lastname: Secades
authors.forename: Juan-Pablo
authors.initials: JP
authors.lastname: Rodrigo
authors.forename: Rubén
authors.initials: R
authors.lastname: Cabanillas
authors.forename: Agustín
authors.initials: A
authors.lastname: Herrero
authors.forename: Carlos
authors.initials: C
authors.lastname: Suarez
authors.forename: María-Dolores
authors.initials: MD
authors.lastname: Chiara
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D018628:Gene Dosage; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019061:src-Family Kinases