Focal adhesion kinase (FAK) gene amplification and its clinical implications in gastric cancer.
Focal adhesion kinase, a nonreceptor tyrosine kinase, is known to be associated with tumor progression in various tumors. Because the clinical implications of focal adhesion kinase overexpression in gastric cancer have been inconsistent, we extended previous studies and evaluated focal adhesion kinase gene amplification as well as its protein expression. Immunohistochemical tissue array analysis showed that focal adhesion kinase immunoreactivity was present in both the cytoplasm and membrane of gastric cancer cells. Diffuse immunoreactivity of focal adhesion kinase protein in cytoplasm or membrane was found in 240 (54%) or 263 (59%) of 444 surgical samples, respectively, and positively correlated with tumor size, depth of tumor infiltration, nodal metastasis, distant metastasis, lymphatic invasion, and venous invasion (P < .001). Regarding focal adhesion kinase gene amplification, fluorescence in situ hybridization analysis showed focal adhesion kinase gene amplification in 34 (8.9%) of 384 gastric cancer specimens, whereas there was no amplification in any case of atrophy, intestinal metaplasia, or adenoma/dysplasia. Focal adhesion kinase gene amplification was positively associated with age (P = .012), tumor size (P = .007), nodal metastasis (P = .021), distant metastasis (P = .029), lymphatic invasion (P = .006), venous invasion (P = .032), and perineural invasion (P = .023). Focal adhesion kinase protein expression and gene amplification were positively correlated with each other, and each of them was found to be an independent poor prognostic factor (P < .01). In conclusion, our results showed that either focal adhesion kinase protein expression or focal adhesion kinase gene amplification was significantly correlated with cancer progression and poor prognosis in gastric cancer. Thus, focal adhesion kinase gene amplification could supplement its protein expression for the diagnosis and treatment of gastric cancer.
Park
Joo Hyun
JH
Department of Anatomy, Seoul National University College of Medicine, Seoul, Korea.
Lee
Byung-Lan
BL
Yoon
Jiyeon
J
Kim
Jin
J
Kim
Min A
MA
Yang
Han-Kwang
HK
Kim
Woo Ho
WH
D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000201:enzymology / Q000473:pathology; D003593:Cytoplasm / Q000201:enzymology / Q000473:pathology; D004273:DNA, Neoplasm / Q000032:analysis; D018450:Disease Progression; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000235:genetics* / Q000378:metabolism; D005784:Gene Amplification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011379:Prognosis; D056910:Republic of Korea / Q000453:epidemiology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D046888:Tissue Array Analysis
D004273:DNA, Neoplasm; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human