Intratumoral neovascularization and growth pattern in early gastric carcinoma

BACKGROUND. The growth pattern of early gastric carcinoma, based on a volumetric analysis, reflects biologic characteristics of the tumor. The authors investigated the microvessel density (MVD), expression of vascular endothelial growth factor (VEGF), and growth patterns in early gastric carcinoma. METHODS. Ninety-four tissue specimens resected from patients with early gastric carcinoma invading the submucosal layer were examined. Microvessel quantification was performed immunohistochemically using a monoclonal antibody against factor VIII-related antigen. VEGF expression was studied using an anti-VEGF polyclonal antibody. Growth patterns were defined as follows: Pen A type: expansively penetrating growth; Pen B type: infiltratively penetrating growth; Super type: superficially spreading growth. RESULTS. The mean MVD was 16.9 (range, 5.2-43.0). MVD was significantly higher in tumors with venous invasion (P < 0.01), lymphatic vessel invasion (P < 0.05), and lymph node metastases (P < 0.05) compared with MVD in tumors without venous or lymphatic vessel invasion or lymph node metastases. The VEGF-positive rate of Pen A type tumors was 66.7% (18 of 27), that Pen B type was 10.0% (1 of 10), that of Super type was 19.4% (6 of 31), and that of the unclassified type was 15.4% (4 of 26). The VEGF-positive rate in patients with Pen A type tumors was significantly higher than that in patients with the other three growth patterns(P < 0.01). MVD in patients with Pen A type tumors (25.9 ± 9.2) was significantly higher than that in patients with Super type tumors (12.6 ± 5.4) (P < 0.01). Patients with Pen A type tumors had a poorer prognosis than patients whose tumors had other growth patterns (P < 0.05). According to multivariate analysis, VEGF expression and lymphatic vessel invasion were significant prognostic factors. CONCLUSIONS. Pen A type gastric carcinoma tends to secrete VEGF, thus inducing tumor angiogenesis and resulting in venous invasion. Intensive follow-up is necessary for patients with Pen A type tumors, because this tumor type has a greater propensity for hematogenous metastasis.