The relation between the growth patterns of gastric carcinoma and the expression 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 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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Taniguchi
K
K
Second Department of Surgery, School of Medicine, Kanazawa University, Kanazawa City, Japan.
Yonemura
Y
Y
Nojima
N
N
Hirono
Y
Y
Fushida
S
S
Fujimura
T
T
Miwa
K
K
Endo
Y
Y
Yamamoto
H
H
Watanabe
H
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015870:Gene Expression; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis*; D060285:Receptors, Autocrine Motility Factor; D011956:Receptors, Cell Surface / Q000032:analysis*; D018121:Receptors, Cytokine / Q000032:analysis*; D055293:Receptors, Urokinase Plasminogen Activator; D013274:Stomach Neoplasms / Q000737:chemistry / Q000473:pathology*; D015996:Survival Rate; D044767:Ubiquitin-Protein Ligases
C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine; D055293:Receptors, Urokinase Plasminogen Activator; C555000:AMFR protein, human; D060285:Receptors, Autocrine Motility Factor; D044767:Ubiquitin-Protein Ligases; D019859:Proto-Oncogene Proteins c-met