Prognostic angiogenic markers(endoglin, VEGF, CD31) and tumor cell proliferation(Ki67) for gastrointestinal stromal tumors

AIM: To evaluate the correlation between the immunoexpression of angiogenic markers [CD31, CD105 and vascular endothelial growth factor(VEGF)], proliferative index(Ki67), and prognosis of patients with gastrointestinal stromal tumors(GIST).METHODS: This is a retrospective study of 54 GIST cases. Medical records were searched to obtain the GIST patients’ demographic and clinical data, and paraffin-embedded blocks of tumor samples were retrieved from the hospital archives to conduct a new immunohistochemical evaluation. The tumor samples of GIST patients were subject to immunohistochemical evaluation for endoglin(CD105), CD31, VEGF, and Ki67 expression. The CD105 and CD31 intratumoral microvascular density(IMVD) was measured using automated analysis. We determined the correlation between the immunoexpression of CD105, CD31, VEGF,Ki67 and prognosis. In addition, we conducted a cutoff analysis using the receiver-operating characteristic curve. VEGF positivity was classified as either null/weak or strong. Ki67 was evaluated using a cutoff of 5%positive cells. The prognosis was classified as good(patient alive without recurrence) or poor(patient with recurrence/death).RESULTS: The distribution of tumor sites among the54 analyzed samples was as follows: 27(50%) in the stomach, 20(37.1%) in the small intestine, 6(11.1%)in the colon, and 1(1.8%) in the esophagus. The size of the tumors ranged from 2 to 33 cm(median: 8cm); in 12 cases(22.2%), the tumor was below 5 cm at the largest diameter, but in 42 cases(77.7%), the tumor was larger than 5 cm. The means of CD105 and CD31 were significantly higher in the group with poor prognosis(P < 0.001). The cut-off values of CD105(>1.2%) and CD31(> 2.5%) in the receiver-operating characteristic curve were related to a poorer prognosis.Cases with a better prognosis showed significantly null/weak staining for VEGF(P < 0.001). Ki-67 expression of≥ 5% was strongly correlated with a worse prognosis(P< 0.001). In the multivariate analysis, CD105 was the variable that most strongly correlated with prognosis.CONCLUSION: The IMVD cutoff values for the angiogenic markers CD105 and CD31, may be prognostic factors for GIST, in addition to VEGF and Ki67.