Taniguchi K, Yonemura Y, Nojima N, Hirono Y, Fushida S, Fujimura T, Miwa K, Endo Y, Yamamoto H, Watanabe H
Second Department of Surgery, School of Medicine, Kanazawa University, Kanazawa City, Japan.
Cancer. 1998 Jun 1;82(11):2112-22.
Hepatocyte growth factor receptor (c-met), autocrine motility factor receptor (AMFR), and urokinase-type plasminogen activator receptor (uPAR) are known to play important roles in tumor cell migration, invasion, and metastasis. The authors studied the relation between the expression patterns of these genes and the growth patterns of human gastric carcinoma.
The relation between the expression of c-met, AMFR, and uPAR and clinicopathologic parameters was studied using immunohistochemical preparations from 102 paraffin embedded primary gastric carcinomas.
Of 102 cases, 43 (42%) had overexpression of c-met, and AMFR and uPAR immunoreactivity was observed in 41 cases (40%) and 38 cases (37%), respectively. Macroscopic examination revealed that all three genes were expressed in 1 (3%) of 32 early stage gastric carcinomas, 0 (0%) of 29 localized carcinomas (Borrmann types 1 and 2), and 16 (39%) of 41 infiltrating carcinomas (Borrmann types 3 and 4). In particular, the incidence (68%, 13 of 19 cases) of simultaneous expression of the three genes was significantly higher in Borrmann type 4 gastric carcinoma than in the other macroscopic types (P < 0.01). The overexpression of these genes was also closely associated with lymph node metastasis and peritoneal dissemination. In addition, the simultaneous overexpression of the three genes was associated with positive lymphatic vessel invasion and infiltrating type. Patients with tumors that simultaneously expressed all three genes had significantly poorer prognoses than those with tumors expressing only one or two of the genes. Furthermore, the number of genes expressed was closely related to the prognosis, and the Cox proportional hazards model identified this as one of the independent prognostic factors.
These results suggest that the expression patterns of c-met, AMFR, and uPAR may be closely associated with the progression and invasion of gastric carcinoma as well as the prognoses of the patients. Borrmann type 4 gastric carcinoma is characterized by the diverse and simultaneous expression of these three genes.
已知肝细胞生长因子受体（c-met）、自分泌运动因子受体（AMFR）和尿激酶型纤溶酶原激活物受体（uPAR）在肿瘤细胞迁移、侵袭和转移中发挥重要作用。作者研究了这些基因的表达模式与人类胃癌生长模式之间的关系。
使用102例石蜡包埋的原发性胃癌的免疫组织化学制剂，研究c-met、AMFR和uPAR的表达与临床病理参数之间的关系。
102例病例中，43例（42%）c-met过表达，41例（40%）观察到AMFR免疫反应性，38例（37%）观察到uPAR免疫反应性。大体检查显示，32例早期胃癌中有1例（3%）表达所有三个基因，29例局限性癌（Borrmann 1型和2型）中0例（0%）表达，41例浸润性癌（Borrmann 3型和4型）中有16例（39%）表达。特别是，Borrmann 4型胃癌中三个基因同时表达的发生率（68%，19例中的13例）显著高于其他大体类型（P < 0.01）。这些基因的过表达也与淋巴结转移和腹膜播散密切相关。此外，三个基因同时过表达与淋巴管浸润阳性和浸润型相关。同时表达所有三个基因的肿瘤患者的预后明显比仅表达一个或两个基因的肿瘤患者差。此外，表达的基因数量与预后密切相关，Cox比例风险模型将其确定为独立的预后因素之一。
这些结果表明，c-met、AMFR和uPAR的表达模式可能与胃癌的进展、侵袭以及患者的预后密切相关。Borrmann 4型胃癌的特征是这三个基因的多样且同时表达。
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