title: Expression of the hypoxia-inducible monocarboxylate transporter MCT4 is increased in triple negative breast cancer and correlates independently with clinical outcome.
abstract: BACKGROUND
  (18)Fluor-deoxy-glucose PET-scanning of glycolytic metabolism is being used for staging in many tumors however its impact on prognosis has never been studied in breast cancer.
  
  
  METHODS
  Glycolytic and hypoxic markers: glucose transporter (GLUT1), carbonic anhydrase IX (CAIX), monocarboxylate transporter 1 and 4 (MCT1, 4), MCT accessory protein basigin and lactate-dehydrogenase A (LDH-A) were assessed by immunohistochemistry in two cohorts of breast cancer comprising 643 node-negative and 127 triple negative breast cancers (TNBC) respectively.
  
  
  RESULTS
  In the 643 node-negative breast tumor cohort with a median follow-up of 124 months, TNBC were the most glycolytic (≈70%), followed by Her-2 (≈50%) and RH-positive cancers (≈30%). Tumoral MCT4 staining (without stromal staining) was a strong independent prognostic factor for metastasis-free survival (HR=0.47, P=0.02) and overall-survival (HR=0.38, P=0.002). These results were confirmed in the independent cohort of 127 cancer patients.
  
  
  CONCLUSIONS
  Glycolytic markers are expressed in all breast tumors with highest expression occurring in TNBC. MCT4, the hypoxia-inducible lactate/H(+) symporter demonstrated the strongest deleterious impact on survival. We propose that MCT4 serves as a new prognostic factor in node-negative breast cancer and can perhaps act soon as a theranostic factor considering the current pharmacological development of MCT4 inhibitors.
authors: Department of Radiation Oncology, Centre A. Lacassagne, Nice, France.
authors: J
authors: J
authors: Doyen
authors: Department of Gynecology, Archet II Hospital, 06202 Nice, France.
authors: C
authors: C
authors: Trastour
authors: Department of Pathology, Centre A. Lacassagne, Nice, France.
authors: F
authors: F
authors: Ettore
authors: Department of Pathology, Centre A. Lacassagne, Nice, France.
authors: I
authors: I
authors: Peyrottes
authors: Department of Pathology, Centre A. Lacassagne, Nice, France.
authors: N
authors: N
authors: Toussant
authors: Department of Medical Statistics, Centre A. Lacassagne, Nice, France.
authors: J
authors: J
authors: Gal
authors: Institute for Research on Cancer & Aging (IRCAN), University of Nice, Centre A. Lacassagne, 06189 Nice, France.
authors: K
authors: K
authors: Ilc
authors: Institute for Research on Cancer & Aging (IRCAN), University of Nice, Centre A. Lacassagne, 06189 Nice, France.
authors: D
authors: D
authors: Roux
authors: Centre Scientifique de Monaco (CSM), Monaco.
authors: S K
authors: SK
authors: Parks
authors: Department of Medical Oncology, Centre A. Lacassagne, Nice, France.
authors: J M
authors: JM
authors: Ferrero
authors: Institute for Research on Cancer & Aging (IRCAN), University of Nice, Centre A. Lacassagne, 06189 Nice, France; Centre Scientifique de Monaco (CSM), Monaco. Electronic address: jacques.pouyssegur@unice.fr.
authors: J
authors: J
authors: Pouysségur
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000378:metabolism; D005260:Female; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D000080864:Lactate Dehydrogenase 5; D008875:Middle Aged; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods; D011237:Predictive Value of Tests; D011379:Prognosis; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D051272:Glucose Transporter Type 1; D007527:Isoenzymes; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; C406962:SLC16A4 protein, human; C495677:SLC2A1 protein, human; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases
keywords: Glycolysis; Hypoxia; MCT4; Monocarboxylate transporters; Triple negative breast cancer