Giaginis Constantinos T, Vgenopoulou Stephanie, Tsourouflis Gerasimos S, Politi Ekaterini N, Kouraklis Gregorios P, Theocharis Stamatios E
Department of Forensic Medicine, Medical School, University of Athens, 75 Mikras Asias street, Goudi, Athens GR11527, Greece.
Pathol Oncol Res. 2009 Jun;15(2):173-81. doi: 10.1007/s12253-008-9120-2. Epub 2008 Nov 6.
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.
黏着斑激酶(FAK)是一种非受体酪氨酸激酶蛋白,作为整合素信号级联反应的早期调节因子,调控基本的细胞功能。在转化细胞中,不受抑制的FAK信号传导被认为可促进肿瘤生长、进展和转移。本研究的目的是评估FAK表达在两种不同组织学类型的人类胃肿瘤中的临床意义。采用免疫组织化学方法评估了66例胃腺癌肿瘤样本中FAK的表达情况,其中肠型30例,弥漫型36例,并对其与各种临床病理特征、肿瘤增殖能力和患者生存率进行了统计学分析。在肠型癌中,FAK表达增强与肿瘤增殖能力增加显著相关(P = 0.012)。在弥漫型癌中,FAK染色强度与肿瘤大小(P = 0.026)和疾病分期(P = 0.024)显著相关,与淋巴结状态也存在临界相关性(P = 0.053)。在弥漫型癌中,FAK表达增强与总生存时间延长显著相关(对数秩检验,P = 0.014),在多因素分析中也被确定为独立的预后因素(Cox回归,P = 0.016)。相比之下,肠型肿瘤且FAK表达增强的患者总生存时间较短,但未达到统计学意义(对数秩检验,P = 0.092)。目前的数据支持FAK蛋白可被视为胃肿瘤诊断和预后标志物的证据。有必要对更大规模的临床样本进行进一步研究,并突出两种组织学类型的不同影响,以阐明FAK蛋白在胃肿瘤中的临床意义。