TY - JOUR
T1 - Subcellular FIH-1 expression patterns in invasive breast cancer in relation to HIF-1a expression
AU - Hyseni, Agon
AU - Van Der Groep, Petra
AU - Van Der Wall, Elsken
AU - Van Diest, Paul J.
PY - 2011/12
Y1 - 2011/12
N2 - Background Hypoxia Inducible Factor-1α (HIF-1α) expression in breast cancer is associated with a poor clinical outcome. HIF-1α shows two expression patterns: the canonical poor prognosis hypoxia-related perinecrotic pattern and a diffuse expression pattern that seems to have less downstream effects and is clearly associated with poor survival. Factor-inhibiting hypoxia-inducible factor 1 (FIH- 1) inhibits HIF-1 activity by hydroxylating the C-terminal trans-activation domain of the HIF-1α subunit, thus preventing HIF-1 from recruiting co-activators CPB/p300, which are important for inducing the transcription of target genes. The aim of this study was to investigate the expression patterns of FIH-1 in breast cancer and evaluate the relationship between FIH-1 and HIF-1α expression in breast cancer as a possible explanation for apparently less downstream effects of diffuse HIF-1α expression. Methods Tissue sections from 92 consecutive invasive breast carcinomas were stained by immunohistochemistry for FIH-1, HIF-1α, glucose transporter 1 (GLUT-1) and carbonic anhydrase IX (CAIX). Results 45 cases overexpressed HIF-1α, 5 of which in a perinecrotic fashion while FIH-1 was positive in 73 of the 92 cases studied. Contrary to our expectations, three out of five cases with perinecrotic HIF-1a expression were also positive for FIH1. Cytoplasmic FIH-1 correlated with HIF-1a expression (P=0.03) and tumor grade (P=0.01). HIF-1a overexpression predicted poorer prognosis as usual (P=0.02). FIH expression had no additional prognostic value to HIF-1a. Conclusions FIH1 is expressed in the majority of invasive breast carcinomas and shows distinct subcellular localization patterns. FIH-1 expression does not seem to explain the proposed functional differences between diffuse and perinecrotic HIF-1α expression in breast cancer.
AB - Background Hypoxia Inducible Factor-1α (HIF-1α) expression in breast cancer is associated with a poor clinical outcome. HIF-1α shows two expression patterns: the canonical poor prognosis hypoxia-related perinecrotic pattern and a diffuse expression pattern that seems to have less downstream effects and is clearly associated with poor survival. Factor-inhibiting hypoxia-inducible factor 1 (FIH- 1) inhibits HIF-1 activity by hydroxylating the C-terminal trans-activation domain of the HIF-1α subunit, thus preventing HIF-1 from recruiting co-activators CPB/p300, which are important for inducing the transcription of target genes. The aim of this study was to investigate the expression patterns of FIH-1 in breast cancer and evaluate the relationship between FIH-1 and HIF-1α expression in breast cancer as a possible explanation for apparently less downstream effects of diffuse HIF-1α expression. Methods Tissue sections from 92 consecutive invasive breast carcinomas were stained by immunohistochemistry for FIH-1, HIF-1α, glucose transporter 1 (GLUT-1) and carbonic anhydrase IX (CAIX). Results 45 cases overexpressed HIF-1α, 5 of which in a perinecrotic fashion while FIH-1 was positive in 73 of the 92 cases studied. Contrary to our expectations, three out of five cases with perinecrotic HIF-1a expression were also positive for FIH1. Cytoplasmic FIH-1 correlated with HIF-1a expression (P=0.03) and tumor grade (P=0.01). HIF-1a overexpression predicted poorer prognosis as usual (P=0.02). FIH expression had no additional prognostic value to HIF-1a. Conclusions FIH1 is expressed in the majority of invasive breast carcinomas and shows distinct subcellular localization patterns. FIH-1 expression does not seem to explain the proposed functional differences between diffuse and perinecrotic HIF-1α expression in breast cancer.
KW - Breast cancer
KW - Hypoxia
KW - Immunohistochemistry
KW - Prognosis
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U2 - 10.1007/s13402-011-0053-5
DO - 10.1007/s13402-011-0053-5
M3 - Article
C2 - 21732131
AN - SCOPUS:84861494579
VL - 34
SP - 565
EP - 570
JO - Cellular oncology (Dordrecht)
JF - Cellular oncology (Dordrecht)
SN - 2211-3428
IS - 6
ER -