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To investigate the relation between necrosis and hypoxia in breast cancer we examined the expression of hypoxia-associated markers HIF1, CA IX and GLUT1 by immunohistochemistry in 97 invasive ductal carcinomas. This selected series comprised 48 tumors with extensive necrosis and 49 control tumors without necrosis. Over 90% of necrotic and 30% of non-necrotic tumors expressed at least one hypoxia marker. We also observed expression of hypoxia associated markers in tumor stroma. Examination of primary human breast fibroblasts in vitro confirmed that CA IX mRNA and protein can be induced by hypoxia. Survival analysis of 53 cases found that the subset of tumors with stromal hypoxia exhibit better prognosis (p=0.027). Our results indicate that necrosis is often accompanied by hypoxia but that hypoxia without necrosis may also be a frequent occurrence. The use of several hypoxia markers may identify a continuum of hypoxia in tumors, which can be sub-classified by different co-expression patterns. We conclude that stromal and epithelial hypoxia may have different biological backgrounds and that stromal hypoxia may affect survival.

Original publication

DOI

10.1023/A:1025476722493

Type

Journal article

Journal

Breast Cancer Res Treat

Publication Date

09/2003

Volume

81

Pages

61 - 69

Keywords

Antigens, Neoplasm, Biomarkers, Tumor, Blotting, Western, Breast Neoplasms, Carbonic Anhydrase IX, Carbonic Anhydrases, Carcinoma, Ductal, Breast, Cell Culture Techniques, Cell Hypoxia, DNA-Binding Proteins, Female, Gene Expression Regulation, Neoplastic, Glucose Transport Proteins, Facilitative, Humans, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit, Immunohistochemistry, Monosaccharide Transport Proteins, Necrosis, Neoplasm Proteins, Nuclear Proteins, Reverse Transcriptase Polymerase Chain Reaction, Survival Analysis, Transcription Factors