Abstract:
:Hypoxia is known to play important role in cancer biology. In sarcomas, hypoxia-induced protein biomarkers such as Hypoxia Inducible Factor-1a (HIF-1a), vascular endothelial growth factor (VEGF), and Erythropoietin (Epo) have been previously reported in only a few studies. Moreover, the biologic significance and relationship to tumorigenesis of these hypoxia-induced biomarkers is not well understood in the context of sarcoma. The HIF negative regulator, Prolyl Hydroxylase Domain protein 2 (PHD2) has not been evaluated in sarcomas. We examined the expression of PHD2, HIF-1a, and several other hypoxia induced biomarkers in a series of clinically characterized, retroperitoneal sarcomas with immunohistochemical methods. Expression of these proteins was analyzed and correlated with clinical outcome. Increased HIF-1a expression was associated with shorter overall and disease free survival. PHD2 expression was detected in the majority of sarcoma cases, with increased expression correlating with high tumor grade but not with survival. Though changes in PHD2 expression alone did not correlate with overall and disease free survival, reduced/absent PHD2 expression in the presence of HIF-1a expression was associated with shorter overall and disease-free survival than that of other HIF-1a/PHD2 expression profiles. These observations suggest that regulation and expression of both PHD2 and HIF-1a are important to the biology of sarcomas, and that loss of PHD2 function has an additional adverse effect in the prognosis of sarcomas in tumors expressing HIF-1a. The biologic and therapeutic implications of HIF-1a and PHD2 expression in retroperitoneal sarcomas warrant further investigation.
journal_name
Cancer Biol Therjournal_title
Cancer biology & therapyauthors
Huang JH,Lee FS,Pasha TL,Sammel MD,Karakousis G,Xu G,Fraker D,Zhang PJdoi
10.4161/cbt.9.4.10744subject
Has Abstractpub_date
2010-02-01 00:00:00pages
303-11issue
4eissn
1538-4047issn
1555-8576pii
10744journal_volume
9pub_type
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