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Open Access Research

Hypoxia-inducible factor-2a is associated with ABCG2 expression, histology-grade and Ki67 expression in breast invasive ductal carcinoma

Lei Xiang1, Zhi-Heng Liu2, Qin Huan3, Peng Su1, Guang-Jun Du1, Yan Wang1, Peng Gao1 and Geng-Yin Zhou1*

Author Affiliations

1 Department of Pathology, School of Medicine, Shandong University, Jinan, Shandong 250012, People's Republic of China

2 Department of Hepatobiliary Surgery, Liaocheng People's Hospital and Liaocheng Clinical School of Taishan Medical University, Liaocheng, Shandong, 252000, People's Republic of China

3 Department of Internal Medicine, Shandong Jiaotong Hospital, Jinan, Shandong 250031, People's Republic of China

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Diagnostic Pathology 2012, 7:32  doi:10.1186/1746-1596-7-32

Published: 27 March 2012

Abstract

Background

Breast cancer is the most common cancer and the leading cause of cancer mortality in women worldwide. Hypoxia is an important factor involved in the progression of solid tumors and has been associated with various indicators of tumor metabolism, angiogenesis and metastasis. But little is known about the contribution of Hypoxia-Inducible Factor-2a (HIF-2a) to the drug resistance and the clinicopathological characteristics in breast cancer.

Methods

Immunohistochemistry was employed on the tissue microarray paraffin sections of surgically removed samples from 196 invasive breast cancer patients with clinicopathological data. The correlations between the expression of HIF-2a and ABCG2 as well as other patients' clinicopathological data were investigated.

Results

The results showed that HIF-2a was expressed in different intensities and distributions in the tumor cells of the breast invasive ductal carcinoma. A positive staining for HIF-2a was defined as a brown staining observed mainly in the nucleus. A statistically significant correlation was demonstrated between HIF-2a expression and ABCG2 expression (p = 0.001), histology-grade (p = 0.029), and Ki67 (p = 0. 043) respectively.

Conclusion

HIF-2a was correlated with ABCG2 expression, histology-grade and Ki67 expression in breast invasive ductal carcinoma. HIF-2a could regulate ABCG2 in breast cancer cells, and could be a novel potential bio-marker to predict chemotherapy effectiveness. The hypoxia/HIF-2a/ABCG2 pathway could be a new mechanism of breast cancer multidrug-resistance.

Virtual slides

http://www.diagnosticpathology.diagnomx.eu/vs/2965948166714795

Keywords:
HIF-2a; ABCG2(BCRP); Histology-grade; Ki67; Breast invasive ductal cancer; IHC; Tissue microarray; MDR