Published in:
01-12-2006 | Original Article
Expression of hypoxia-inducible factor (HIF)-1α as a biomarker of outcome in soft-tissue sarcomas
Authors:
Ken Shintani, Akihiko Matsumine, Katsuyuki Kusuzaki, Takao Matsubara, Haruhiko Satonaka, Toru Wakabayashi, Yoko Hoki, Atsumasa Uchida
Published in:
Virchows Archiv
|
Issue 6/2006
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Abstract
Hypoxia-inducible factor (HIF)-1α is a transcription factor that supports the adaptation of human cancer cells to hypoxia and tumor growth and progression. The overexpression of HIF-1α protein has been reported to be associated with a worse prognosis in various cancers. However, the expression of HIF-1α in soft-tissue sarcomas has not yet been characterized. The expression of HIF-1α protein was immunohistochemically determined in 49 specimens of soft-tissue sarcomas including malignant fibrous histiocytoma (29 patients), synovial sarcoma (12 patients), leiomyosarcoma (four patients), and malignant peripheral nerve sheath tumors (four patients). The 49 samples consisted of 40 primary lesions and nine local recurrences. An immunohistochemical analysis showed the nuclear accumulation of HIF-1α protein in 35 (71.4%) samples. The expression of HIF-1α was negative in 14 (28.6%) cases, weak in nine (18.4%), moderate in 17 (35.4%), and strong in nine (18.4%). The patients with a strong or moderate expression of HIF-1α had a significantly shorter overall survival rate in comparison with those with a weak or negative expression in a univariate analysis (P = 0.029; log-rank test) and multivariate analysis (P = 0.018). This is the first report that demonstrated an overexpression of HIF-1α protein to be an independent prognostic factor for soft-tissue sarcomas.