Department of Anatomy, Seoul National University College of Medicine, Seoul, Korea.
Hum Pathol. 2010 Dec;41(12):1664-73. doi: 10.1016/j.humpath.2010.06.004. Epub 2010 Sep 24.
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.
黏着斑激酶是一种非受体酪氨酸激酶，已知与多种肿瘤的肿瘤进展有关。由于黏着斑激酶在胃癌中的过表达的临床意义一直不一致，我们扩展了以前的研究，并评估了黏着斑激酶基因扩增及其蛋白表达。免疫组织化学组织微阵列分析显示，黏着斑激酶免疫反应性存在于胃癌细胞的细胞质和膜中。在 444 例手术样本中，分别有 240 例（54%）或 263 例（59%）出现细胞质或膜中黏着斑激酶蛋白弥漫性免疫反应，且与肿瘤大小、肿瘤浸润深度、淋巴结转移、远处转移、淋巴浸润和静脉浸润呈正相关（P <.001）。关于黏着斑激酶基因扩增，荧光原位杂交分析显示 384 例胃癌标本中有 34 例（8.9%）存在黏着斑激酶基因扩增，而在任何萎缩、肠上皮化生或腺瘤/发育不良的病例中均无扩增。黏着斑激酶基因扩增与年龄（P =.012）、肿瘤大小（P =.007）、淋巴结转移（P =.021）、远处转移（P =.029）、淋巴浸润（P =.006）、静脉浸润（P =.032）和神经周围浸润（P =.023）呈正相关。黏着斑激酶蛋白表达和基因扩增彼此呈正相关，且两者均为独立的预后不良因素（P <.01）。总之，我们的研究结果表明，黏着斑激酶蛋白表达或基因扩增均与胃癌的进展和不良预后显著相关。因此，黏着斑激酶基因扩增可以补充其蛋白表达，用于胃癌的诊断和治疗。
