© 2005 Foundation for Promotion of Cancer Research
Hypoxia-inducible Factor-1
is Associated with Risk of Aggressive Behavior and Tumor Angiogenesis in Gastrointestinal Stromal Tumor
1 Department of Pathology and 2 Department of Radiation Therapy, Kaohsiung Medical University Chung-Ho Memorial Hospital and 3 Graduate Institute of Occupational Safety and Health, Kaohsiung Medical University, Kaohsiung, Taiwan
For reprints and all correspondence: Chee-Yin Chai, Department of Pathology, Kaohsiung Medical University Chung-Ho Memorial Hospital, No. 100, Tzyou 1st Road, Kaohsiung City 807, Taiwan. E-mail: cychai{at}kmu.edu.tw
Received December 20, 2004; accepted March 9, 2005
Background: The objective of this study was to evaluate the relationship of HIF-1
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 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 
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 (P<0.0001). In addition, the incidence of recurrence/distant metastasis was significantly higher in cases of high HIF-1 expression (12/35; 34.3%) than in cases of low HIF-1 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 expression tumors than in low-expression tumors (P < 0.0001).
Conclusions: Our findings suggest that HIF-1 may play an important role in aggressive behavior and tumor angiogenesis in GIST. In addition, high expression of HIF-1 was significantly correlated with tumor recurrence/distant metastasis, so it may provide an ancillary prognostic factor for GIST.
Key Words: gastrointestinal stromal tumor • hypoxia inducible factor-1 alpha (HIF-1) • immunohistochemistry, microvessel density (MVD) • vascular endothelial growth factor (VEGF)
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