Hypoxia-inducible Factor-1α is Associated with Risk of Aggressive Behavior and Tumor Angiogenesis in Gastrointestinal Stromal Tumor

Abstract

Background: The objective of this study was to evaluate the relationship of HIF-1α 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-1α and analyzed correlation with tumor angiogenesis monitored by expression of vascular endothelial growth factor (VEGF) and tumor microvessel density using immunohistochemical staining. The data were analyzed with χ² 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-1α (P<0.0001). In addition, the incidence of recurrence/distant metastasis was significantly higher in cases of high HIF-1α expression (12/35; 34.3%) than in cases of low HIF-1α 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-1α expression tumors than in low-expression tumors (P < 0.0001).

Conclusions: Our findings suggest that HIF-1α may play an important role in aggressive behavior and tumor angiogenesis in GIST. In addition, high expression of HIF-1α was significantly correlated with tumor recurrence/distant metastasis, so it may provide an ancillary prognostic factor for GIST.

gastrointestinal stromal tumor, hypoxia inducible factor-1 alpha (HIF-1α), immunohistochemistry, microvessel density (MVD), vascular endothelial growth factor (VEGF)