Li Xiaohan, Zheng Huachuan, Hara Takuo, Takahashi Hiroyuki, Masuda Shinji, Wang Zhigang, Yang Xianghong, Guan Yifu, Takano Yasuo
Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, P.R. China.
Int J Oncol. 2008 Jul;33(1):69-79.
Tumor metastasis depends on cell adhesiveness, motility and deformability, resulting from quantitative alterations and rearrangement of various actin-binding cytoskeletal components, such as cortactin and fascin. To clarify the involvement of cortactin and fascin expression in tumorigenesis and progression of gastric carcinoma, we performed immunohistochemistry (IHC) on tissue microarray containing gastric carcinomas, adenomas and adjacent non-neoplastic mucosa (ANNM) using the antibodies against cortactin (Ab-466, -421) and fascin as well as a comparison of their expression with clinicopathological parameters of the tumors. Gastric carcinoma cell lines MKN28, AGS, MKN45, KATO-III and HGC-27 were studied for both proteins by IHC. Cortactin-466 was found to be highly expressed in adenoma, compared with ANNMs and carcinoma (p<0.05), and more frequently in ANNMs than in carcinoma (p<0.05). Cortactin-421 expression was higher in gastric carcinomas than in adenoma and ANNMs (p<0.05). There was increased fascin expression in gastric carcinoma and adenoma than in ANNMs (p<0.05). Most of the gastric carcinoma cell lines showed expression of cortactin and fascin at different levels. Cortactin-466 expression was inversely correlated with tumor size, depth of invasion, lymphatic and venous invasion, lymph node metastasis and UICC staging (p<0.05). The converse was observed for cortactin-421 and fascin (p<0.05). There was stronger positivity of both cortactins in intestinal- versus diffuse-type carcinomas (p<0.05). Univariate analysis indicated the cumulative survival rate of patients with positive cortactin-466 expression to be higher than without its expression even stratified according to the depth of invasion (p<0.05). However, it was the converse for fascin (p<0.05). Multivariate analysis showed that age, depth of invasion, lymphatic invasion, lymph node metastasis, UICC staging and Lauren's classification were independent prognostic factors for carcinomas (p<0.05). It was suggested that aberrant expression of cortactin and fascin possibly contributes to the pathogenesis, growth, invasion and metastasis of gastric carcinomas. Thus, they may be objective and effective markers to indicate the pathobiological behaviors and prognosis of gastric carcinomas.
肿瘤转移取决于细胞黏附性、运动性和可变形性，这是由各种肌动蛋白结合细胞骨架成分（如皮层肌动蛋白和丝状肌动蛋白）的定量改变和重排所导致的。为了阐明皮层肌动蛋白和丝状肌动蛋白表达在胃癌发生和进展中的作用，我们使用针对皮层肌动蛋白（Ab - 466、- 421）和丝状肌动蛋白的抗体，对包含胃癌、腺瘤及相邻非肿瘤性黏膜（ANNM）的组织芯片进行了免疫组织化学（IHC）检测，并将它们的表达与肿瘤的临床病理参数进行了比较。通过IHC对胃癌细胞系MKN28、AGS、MKN45、KATO - III和HGC - 27进行了这两种蛋白的研究。发现皮层肌动蛋白 - 466在腺瘤中高表达，与ANNM和癌相比（p < 0.05），且在ANNM中比在癌中更常见（p < 0.05）。皮层肌动蛋白 - 421在胃癌中的表达高于腺瘤和ANNM（p < 0.05）。胃癌和腺瘤中丝状肌动蛋白的表达高于ANNM（p < 0.05）。大多数胃癌细胞系显示出不同水平的皮层肌动蛋白和丝状肌动蛋白表达。皮层肌动蛋白 - 466的表达与肿瘤大小、浸润深度、淋巴管和静脉浸润、淋巴结转移及UICC分期呈负相关（p < 0.05）。皮层肌动蛋白 - 421和丝状肌动蛋白则相反（p < 0.05）。在肠型与弥漫型癌中，两种皮层肌动蛋白的阳性更强（p < 0.05）。单因素分析表明，即使根据浸润深度分层，皮层肌动蛋白 - 466表达阳性患者的累积生存率也高于无该表达者（p < 0.05）。然而，丝状肌动蛋白情况相反（p < 0.05）。多因素分析显示，年龄、浸润深度、淋巴管浸润、淋巴结转移、UICC分期和劳伦分类是癌的独立预后因素（p < 0.05）。提示皮层肌动蛋白和丝状肌动蛋白的异常表达可能有助于胃癌的发病机制、生长、浸润和转移。因此，它们可能是指示胃癌病理生物学行为和预后的客观有效标志物。
