Aug 31, 2011

Expressions of individual PHDs associate with good prognostic factors and increased proliferation in breast cancer patients

Breast Cancer Research and Treatment
Emmi PeuralaArja Jukkola-Vuorinen

Abstract

Tumor hypoxia-inducible transcription factor (HIF) overexpression often associates with a poor prognosis. Stability of the HIF-α subunits is regulated by HIF prolyl 4-hydroxylases, PHD1-3. We assessed here immunohistochemical expression of PHD1-3 and HIF-1α and 2α in patients with invasive ductal breast carcinoma (n = 102) and correlated their expression levels with main clinical prognostic factors and survival. PHD1 expression correlated with high proliferation, and these tumors were mainly estrogen receptor-negative. PHD3 expression declined in tumors of large size, poor differentiation, and high proliferation. There was a tendency for increased breast cancer-specific survival and longer disease-free survival among patients with high tumor PHD2 expression. Surprisingly, PHD1-3 expression did not correlate with HIF-1α or HIF-2α downregulation. However, HIF-2α expression correlated independently with low tumor stage and HIF-1α expression had a tendency for decreased breast cancer-specific survival. PHD1 and 3 appear to be HIF-independent factors in breast cancer. Not all PHD1 associated proliferation is estrogen-dependent and it is associated with a poor prognosis of cancer. PHD3 may be an important regulator of apoptosis and i...Continue Reading

  • References36
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Mentioned in this Paper

Epas1 protein, mouse
Gene Expression Regulation, Neoplastic
EGLN1
EGLN1 protein, human
Kaplan-Meier Estimate
Neoplasms
Incidence Studies
HIF1alpha protein
Cell Nucleus
Gene Expression

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