Expression and Clinical Significance of Focal Adhesion Kinase in the Two Distinct Histological Types, Intestinal and Diffuse, of Human Gastric Adenocarcinoma

被引:37
作者
Giaginis, Constantinos T. [1 ,2 ]
Vgenopoulou, Stephanie [1 ]
Tsourouflis, Gerasimos S. [2 ]
Politi, Ekaterini N. [1 ,3 ]
Kouraklis, Gregorios P. [2 ]
Theocharis, Stamatios E. [1 ]
机构
[1] Univ Athens, Sch Med, Dept Forens Med & Toxicol, GR-11527 Athens, Greece
[2] Univ Athens, Sch Med, Dept Propedeut Surg 2, GR-11527 Athens, Greece
[3] Univ Athens, Sch Med, Dept Pathol, GR-11527 Athens, Greece
关键词
Clinicopathological parameters; Diffuse; Focal adhesion kinase; Gastric cancer; Immunohistochemistry; Intestinal; Patients' survival; SQUAMOUS-CELL CARCINOMA; HEPATOCELLULAR-CARCINOMA; MOLECULAR-BIOLOGY; TYROSINE KINASE; BREAST-CANCER; LUNG-CANCER; IN-VIVO; OVEREXPRESSION; PHOSPHORYLATION; ACTIVATION;
D O I
10.1007/s12253-008-9120-2
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Focal adhesion kinase (FAK), a non-receptor tyrosine kinase protein, acts as an early modulator of integrin signaling cascade, regulating basic cellular functions. In transformed cells, unopposed FAK signaling has been considered to promote tumor growth, progression and metastasis. The aim of this study was to assess the clinical significance of FAK expression in the two distinct histological types of human gastric neoplasia. FAK expression was assessed immunohistochemically in tumoral samples of 66 gastric adenocarcinoma cases, 30 intestinal and 36 diffuse type, and was statistically analyzed in relation to various clinicopathological characteristics, tumor proliferative capacity and patients' survival. In intestinal type carcinomas, enhanced FAK expression was significantly associated with increased tumor proliferative capacity (P = 0.012). In diffuse type carcinomas, FAK staining intensity was significantly correlated with tumor size (P = 0.026) and disease stage (P = 0.024), presenting also a borderline association with nodal status (P = 0.053). In diffuse type carcinomas, enhanced FAK expression was significantly associated with longer overall survival times (log-rank test, P = 0.014), being also identified as an independent prognostic factor in multivariate analysis (Cox regression, P = 0.016). In contrast, patients with intestinal type tumors and enhanced FAK expression were characterized by shorter overall survival times, without though reaching statistical significance (log-rank test, P = 0.092). The current data support evidence that FAK protein may be considered as a diagnostic and prognostic marker in gastric neoplasia. Further studies conducted on larger clinical samples and highlighting on the distinct impact of the two histological types are warranted to delineate the clinical significance of FAK protein in gastric neoplasia.
引用
收藏
页码:173 / 181
页数:9
相关论文
共 48 条
[1]
[Anonymous], 1997, J CLIN PATHOL
[2]
Cance WG, 2000, CLIN CANCER RES, V6, P2417
[3]
Overexpression of focal adhesion kinase in head and neck squamous cell carcinoma is independent of fak gene copy number [J].
Canel, Marta ;
Secades, Pablo ;
Rodrigo, Juan-Pablo ;
Cabanillas, Ruben ;
Herrero, Agustin ;
Suarez, Carlos ;
Chiara, Maria-Dolores .
CLINICAL CANCER RESEARCH, 2006, 12 (11) :3272-3279
[4]
Up-regulation of focal adhesion kinase in non-small cell lung cancer [J].
Carelli, Stephana ;
Zadra, Giorgia ;
Vaira, Valentina ;
Falleni, Monica ;
Bottiglieri, Luca ;
Nosotti, Mario ;
Di Giulio, Anna Maria ;
Gorio, Alfredo ;
Bosari, Silvano .
LUNG CANCER, 2006, 53 (03) :263-271
[5]
Cary LA, 1996, J CELL SCI, V109, P1787
[6]
Molecular biology of gastric cancer [J].
Cervantes, A. ;
Braun, E. Rodriguez ;
Fidalgo, A. Perez ;
Gonzalez, I. Chirivella .
CLINICAL & TRANSLATIONAL ONCOLOGY, 2007, 9 (04) :208-215
[7]
Disruption of FAK signaling: A side mechanism in cytotoxicity [J].
Chatzizacharias, Nikolaos A. ;
KourakliS, Gregory P. ;
Theocharis, Stamatios E. .
TOXICOLOGY, 2008, 245 (1-2) :1-10
[8]
Chatzizacharias NA, 2008, HISTOL HISTOPATHOL, V23, P629, DOI 10.14670/HH-23.629
[9]
Focal adhesion kinase: a promising target for anticancer therapy [J].
Chatzizacharias, Nikolaos A. ;
Kouraklis, Gregory P. ;
Theocharis, Stamatios E. .
EXPERT OPINION ON THERAPEUTIC TARGETS, 2007, 11 (10) :1315-1328
[10]
New concepts regarding focal promotion of cell migration adhesion kinase and proliferation [J].
Cox, Braden D. ;
Natarajan, Meera ;
Stettner, Michelle R. ;
Gladson, Candece L. .
JOURNAL OF CELLULAR BIOCHEMISTRY, 2006, 99 (01) :36-52