THE RELATION BETWEEN THE GROWTH-PATTERNS OF GASTRIC-CARCINOMA AND THEEXPRESSION OF HEPATOCYTE GROWTH-FACTOR RECEPTOR (C-MET), AUTOCRINE MOTILITY FACTOR-RECEPTOR, AND UROKINASE-TYPE PLASMINOGEN-ACTIVATOR RECEPTOR

BACKGROUND. Hepatocyte growth factor receptor (c-met), autocrine motil ity factor receptor (AMFR), and urokinase-type plasminogen activator r eceptor (uPAR) are known to play important roles in tumor cell migrati on, invasion, and metastasis. The authors studied the relation between the expression patterns of these genes and the growth patterns of hum an gastric carcinoma. METHODS. The relation between the expression of c-met, AMFR, and uPAR and clinicopathologic parameters was studied usi ng immunohistochemical preparations from 102 paraffin embedded primary gastric carcinomas. RESULTS. Of 102 cases, 43 (42%) had overexpressio n of c-met, and AMFR and uPAR immunoreactivity was observed in 41 case s (40%) and 38 cases (37%), respectively. Macroscopic examination reve aled that all three genes were expressed in 1 (3%) of 32 early stage g astric 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 simultan eous expression of the three genes was significantly higher in Borrman n type 4 gastric carcinoma than in the other macroscopic types (P < 0. 01). The overexpression of these genes was also closely associated wit h lymph node metastasis and peritoneal dissemination. In addition, the simultaneous overexpression of the three genes was associated with po sitive 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 rel ated to the prognosis, and the Cox proportional hazards model identifi ed this as one of the independent prognostic factors. CONCLUSIONS. The se results suggest that the expression patterns of c-met, AMFR, and uP AR may be closely associated with the progression and invasion of gast ric carcinoma as well as the prognoses of the patients. Borrmann type 4 gastric carcinoma is characterized by the diverse and simultaneous e xpression of these three genes. (C) 1998 American Cancer Society.