skip to main content

SciTech ConnectSciTech Connect

Title: Expression of the hypoxia-inducible monocarboxylate transporter MCT4 is increased in triple negative breast cancer and correlates independently with clinical outcome

Highlights: • Glycolytic markers are highly expressed in triple negative breast cancers. • Lactate/H{sup +} symporter MCT4 demonstrated the strongest deleterious impact on survival. • MCT4 should serve as a new prognostic factor in node-negative breast cancers. - Abstract: Background: {sup 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. Conclusion: Glycolytic markers are expressed in all breast tumors with highest expression occurring in TNBC. MCT4,more » the hypoxia-inducible lactate/H{sup +} 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.« less
Authors:
 [1] ;  [2] ; ; ;  [3] ;  [4] ; ;  [5] ;  [6] ;  [7] ;  [5] ;  [8]
  1. Department of Radiation Oncology, Centre A. Lacassagne, Nice (France)
  2. Department of Gynecology, Archet II Hospital, 06202 Nice (France)
  3. Department of Pathology, Centre A. Lacassagne, Nice (France)
  4. Department of Medical Statistics, Centre A. Lacassagne, Nice (France)
  5. Institute for Research on Cancer and Aging (IRCAN), University of Nice, Centre A. Lacassagne, 06189 Nice (France)
  6. Centre Scientifique de Monaco (CSM) (Monaco)
  7. Department of Medical Oncology, Centre A. Lacassagne, Nice (France)
  8. (CSM) (Monaco)
Publication Date:
OSTI Identifier:
22416709
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 451; Journal Issue: 1; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANOXIA; CARBONIC ANHYDRASE; GLUCOSE; GLYCOLYSIS; HYDROGEN IONS 1 PLUS; LACTATE DEHYDROGENASE; LACTATES; MAMMARY GLANDS; METASTASES; NEOPLASMS; PATIENTS; POSITRON COMPUTED TOMOGRAPHY; STAINS