Prognostic significance of angiogenesis in gastrointestinal stromal tumor.
Angiogenesis is important in the growth and metastasis of various kinds of solid tumors. To investigate the potential role of angiogenesis in gastrointestinal stromal tumor (GIST), an immunohistochemical analysis was performed in 95 cases of GISTs for microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression. MVD was evaluated with immunohistochemical staining for CD31. A high level of MVD was significantly correlated with overexpression of VEGF, tumor location (intestine>stomach), tumor size (> or =5 cm), tumor grade (high>intermediate>low grade) (P=<0.0001, 0.0422, 0.0006, 0.0359, respectively). Of the 70 GISTs analyzed, KIT exon 11 mutations were detected in 45 cases (64.3%) and KIT exon 9 mutations in two cases (2.9%). No mutations were found in KIT exons 13 and 17, and platelet-derived growth factor receptor-alpha exons 12 and 18. Interestingly, VEGF expression level was significantly higher in the non-KIT exon 11 mutant group than in the KIT exon 11 mutant group (P=0.0266). In univariate analysis, tumor grade (high grade), tumor size (> or =5 cm), mitotic count (> or =5/50 high-power fields), Ki-67 labeling index (> or =4.6%), MVD (> or =7.0/0.95 mm(2)) and VEGF expression (high) were significantly associated with a shorter period of disease-free survival (P=<0.0001, 0.0199, 0.0055 0.0027, 0.0028 and 0.0302, respectively). In multivariate analysis, tumor grade and MVD were identified as independent worse prognostic factors (P=0.0007, 0.0152, respectively). In conclusion, our results suggest that the evaluation of MVD and VEGF expression is useful for predicting the aggressive biologic behavior of GIST, and that angiogenesis associated with VEGF may play an important role, at least in part, in the progression of GIST.
Imamura
Masakazu
M
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Higashiku, Fukuoka, Japan.
Yamamoto
Hidetaka
H
Nakamura
Norimoto
N
Oda
Yoshinao
Y
Yao
Takashi
T
Kakeji
Yoshihiro
Y
Baba
Hideo
H
Maehara
Yoshihiko
Y
Tsuneyoshi
Masazumi
M
D000368:Aged; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000098:blood supply* / Q000235:genetics / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000473:pathology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha