Prognostic significance of angiogenesis in gastrointestinal stromal tumor

Abstract

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 (intestine4stomach), tumor size (Z5 cm), tumor grade (high4intermediate4low grade) (P ¼ o0.0001, 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 ¼ 0.0266). In univariate analysis, tumor grade (high grade), tumor size (Z5 cm), mitotic count (Z5/50 high-power fields), Ki-67 labeling index (Z4.6%), MVD (Z7.0/0.95 mm 2 ) and VEGF expression (high) were significantly associated with a shorter period of disease-free survival (P ¼ o0.0001, 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 ¼ 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. Modern Pathology (2007) 20, 529-537.

Study on relationship between angiogenesis and micrometastases of peripheral blood in breast cancer

“…The more blood vessels in tumor tissues are the higher incidence for tumor cells to enter circulation. MVD in breast cancer tissues is closely related to distant metastasis and survival time, having been conWrmed in similar researches on stomach cancer, melanoma, non-small cell lung cancer and prostate cancer (Zhu et al 2005;Imamura et al 2007;Bono et al 2002). Ohta et al (2001) assessed the association of VEGF with occult micrometastasis in 285 cases with lung cancer.…”

Cabozantinib Is Active against Human Gastrointestinal Stromal Tumor Xenografts Carrying Different KIT Mutations

“…Cabozantinib is known to be a potent antiangiogenic compound, which is likely a result of its inhibitory effect on kinases, including VEGFR2 MET, and AXL (12,13). In GIST, a high MVD is correlated with tumor burden, VEGF expression, and cell proliferation and was shown to be a poor prognostic factor (29). In our models, cabozantinib led to a significant reduction in microvascularization, as assessed by CD31 immunostaining, and the effect was more pronounced than that in imatinib-treated tumors.…”

Microvascular density and endothelial area correlate with Ki-67 proliferative index in surgically-treated pancreatic ductal adenocarcinoma patients

“…MVD and EA have been experimentally proposed to be biomarkers associated with biological aggressiveness and clinical outcome in animal and human malignancies. In regards to pancreatic cancer, it has been established that angiogenesis has a role in its development and progression (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). In addition, Ki-67 expression is an important parameter for biological aggressiveness and prognosis in tumour tissue; Ki-67 antigens are initially expressed in S-phase and increase throughout S-and G 2 -phase until they reach their peak expression during mitosis.…”