Necrosis and hypoxia in invasive breast carcinoma.
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.
Tomes
Ladislav
L
Faculty of Medicine, Department of Pathology, University of Manitoba, Winnipeg, MB, Canada. pwatson@cc.umanitoba.ca
Emberley
Ethan
E
Niu
Yulian
Y
Troup
Sandra
S
Pastorek
Jaromir
J
Strange
Karen
K
Harris
Adrian
A
Watson
Peter H
PH
D000951:Antigens, Neoplasm / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000032:analysis; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry* / Q000473:pathology*; D018929:Cell Culture Techniques; D015687:Cell Hypoxia; D004268:DNA-Binding Proteins / Q000032:analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D051246:Glucose Transport Proteins, Facilitative; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007150:Immunohistochemistry; D009004:Monosaccharide Transport Proteins / Q000032:analysis; D009336:Necrosis; D009363:Neoplasm Proteins / Q000032:analysis; D009687:Nuclear Proteins / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D014157:Transcription Factors
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D051246:Glucose Transport Proteins, Facilitative; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009004:Monosaccharide Transport Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C430746:SLC2A10 protein, human; D014157:Transcription Factors; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases