Hypoxia-inducible factor-1α is associated with risk of aggressive behavior and tumor angiogenesis in gastrointestinal stromal tumor

Background: The objective of this study was to evaluate the relationship of HIF-1 alpha expression and tumor angiogenesis, recurrence/distant metastasis, and its value in the prediction of aggressive behavior of gastrointestinal stromal tumor (GIST). Methods: Paraffin-embedded specimens from 62 patients with GIST were divided into two groups, low risk (n = 31) and high risk (n = 31) according to the tumor size, mitotic count and proliferating cell nuclear antigen (PCNA) index. We investigated the expression of the HIF-1 alpha and analyzed correlation with tumor angiogenesis monitored by expression of vascular endlothelial growth factor (VEGF) and tumor microvessel density using immunohistochemical staining. The data were analyzed with chi(2) test or Fisher's exact test and multivariate test. Results: There were statistically significant differences between high risk (29/31; 93.5%) and low risk (8/31; 25.8%) of GIST in high expression of HIF-1 alpha (P < 0.0001). In addition, the incidence of recurrence/distant metastasis was significantly higher in cases of high HIF-1 alpha expression (12/35; 34.3%) than in cases of low HIF-1 alpha expression (1/24; 4.2%)(P = 0.009). Moreover, high VEGF expression (37/43; 86.0%) and microvessel density (30/32; 93.8%) were significantly higher in high HIF-1 alpha expression tumors than in low-expression tumors (P < 0.0001). Conclusions: Our findings suggest that HIF-1 alpha may play an important role in aggressive behavior and tumor angiogenesis in GIST. In addition, high expression of HIF-1 alpha was significantly correlated with tumor recurrence/distant metastasis, so it may provide an ancillary prognostic factor for GIST.