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Metabolic phenotypes in triple-negative breast cancer

 Sewha Kim  ;  Do Hee Kim  ;  Woo-Hee Jung  ;  Ja Seung Koo 
 TUMOR BIOLOGY, Vol.34(3) : 1699-1712, 2013 
Journal Title
Issue Date
Adult ; Autophagy ; Biomarkers, Tumor/metabolism* ; Breast Neoplasms/classification* ; Breast Neoplasms/metabolism ; Breast Neoplasms/mortality ; Breast Neoplasms/pathology ; Female ; Fibroblasts/metabolism* ; Fibroblasts/pathology ; Glycolysis* ; Humans ; Immunoenzyme Techniques ; Lymphatic Metastasis ; Middle Aged ; Mitochondria/metabolism* ; Mitochondria/pathology ; Neoplasm Grading ; Neoplasm Staging ; Phenotype ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Stromal Cells/metabolism* ; Stromal Cells/pathology ; Survival Rate ; Tissue Array Analysis
Breast cancer ; Reverse Warburg effect ; Triple negative ; Warburg effect
The aim of study was to investigate the metabolism of tumor and stromal cells necessary to determine differential tumor–stroma metabolic interactions according to the molecular subtypes of triple-negative breast cancer (TNBC). Tissues from 132 patients of TNBC were prepared for use as tissue microarrays (TMA). Expression of CK5/6, EGFR, claudin 3, claudin 4, claudin7, E-cadherin, AR, GGT1, STAT1, and interleukin-8 was evaluated by immunohistochemical staining using TMA to classify molecular subtypes of TNBC. In addition, immunohistochemical staining for Glut1, CAIX, BNIP3, MCT4, Beclin-1, LC3A, LC3B, and p62 was performed. According to glycolytic status determined by the immunohistochemical expression of Glut-1 and CAIX in tumor and stroma, the metabolic phenotypes of the TNBCs were defined as follows: Warburg type (tumor: glycolysis, stroma: non-glycolysis), reverse Warburg type (tumor: non-glycolysis, stroma: glycolysis), mixed metabolic type (tumor: glycolysis, stroma: glycolysis), and metabolic null type (tumor: non-glycolysis, stroma: non-glycolysis). TNBCs were classified as follows: 79 Warburg type (59.8 %), 7 reverse Warburg type (5.3 %), 24 mixed metabolic type (18.2 %), and 22 metabolic null type (16.7 %). There was no statistical significance between the metabolic phenotypes and molecular subtypes (P = 0.706). Reverse Warburg type showed the most dysfunctional mitochondrial status for stromal cells, while Warburg type showed the most functional mitochondrial status (P = 0.036). Regarding stromal autophagy status, reverse Warburg type showed the most activated status, while all of the Warburg and metabolic null types showed a non-activated status (P < 0.001). In conclusion, Warburg type was the most common metabolic phenotype in TNBC, while reverse Warburg type was the most unusual. Metabolic phenotypes did not differ among the molecular subtypes of TNBCs.
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1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Koo, Ja Seung(구자승) ORCID logo https://orcid.org/0000-0003-4546-4709
Jung, Woo Hee(정우희)
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