Ito Reiko, Oue Naohide, Zhu Xudong, Yoshida Kazuhiro, Nakayama Hirofumi, Yokozaki Hiroshi, Yasui Wataru
Department of Molecular Pathology, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Virchows Arch. 2003 Feb;442(2):118-23. doi: 10.1007/s00428-002-0718-6. Epub 2002 Dec 14.
Integrin-linked kinase (ILK), a serine/threonine protein kinase, implicates in cellular control of cell-matrix interactions and cell proliferation that is associated with a highly invasive phenotype of certain tumors. To study whether ILK is involved in the development and progression of gastric carcinoma, we examined the expression of ILK in gastric carcinoma cell lines, primary gastric carcinomas and corresponding non-neoplastic mucosa using reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry and analyzed the relationship with clinicopathological parameters. The expression of ILK mRNA was detected in 4 of 5 gastric carcinoma cell lines and 22 of 35 (63%) microdissected tumor samples of primary gastric carcinoma using RT-PCR. The incidence of cases with ILK mRNA expression was significantly higher in scirrhous and intermediate type (82%) than in medullary type (44%) (P=0.0204). Significant association was detected between ILK mRNA expression and presence of nodal metastasis (P=0.0388). Immunohistochemically, strong expression of ILK protein (over 50% of tumor cells were positive) was detected in 69% (84/122) of primary gastric carcinomas, whereas no ILK expression was found in non-neoplastic gastric epithelia. Strong expression of ILK protein was significantly associated with scirrhous and intermediate type (P=0.0217), deep invasion of tumor cells in gastric wall (P=0.0006), and presence of nodal metastasis (P=0.0176). These results strongly suggest that ILK may participate not only in stomach carcinogenesis especially of scirrhous and intermediate types but also in invasion and metastasis of gastric carcinoma. ILK might be a novel molecular marker for aggressive gastric cancer.
整合素连接激酶（ILK）是一种丝氨酸/苏氨酸蛋白激酶，参与细胞对细胞-基质相互作用和细胞增殖的调控，而这与某些肿瘤的高侵袭性表型相关。为研究ILK是否参与胃癌的发生发展，我们采用逆转录聚合酶链反应（RT-PCR）和免疫组织化学方法检测了ILK在胃癌细胞系、原发性胃癌及相应非肿瘤性黏膜中的表达，并分析其与临床病理参数的关系。通过RT-PCR在5个胃癌细胞系中的4个以及35个原发性胃癌显微切割肿瘤样本中的22个（63%）检测到了ILK mRNA的表达。ILK mRNA表达病例的发生率在硬癌和中间型（82%）显著高于髓样型（44%）（P=0.0204）。ILK mRNA表达与淋巴结转移的存在之间存在显著关联（P=0.0388）。免疫组织化学结果显示，69%（84/122）的原发性胃癌中检测到ILK蛋白的强表达（超过50%的肿瘤细胞呈阳性），而在非肿瘤性胃上皮中未发现ILK表达。ILK蛋白的强表达与硬癌和中间型显著相关（P=0.0217）、肿瘤细胞在胃壁的深度浸润显著相关（P=0.0006）以及淋巴结转移的存在显著相关（P=0.0176）。这些结果强烈提示，ILK可能不仅参与胃癌尤其是硬癌和中间型的发生，还参与胃癌的侵袭和转移。ILK可能是侵袭性胃癌的一种新型分子标志物。
