J Doyen1, C Trastour2, F Ettore3, I Peyrottes3, N Toussant3, J Gal4, K Ilc5, D Roux5, S K Parks6, J M Ferrero7, J Pouysségur8. 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 & 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. 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.
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. CONCLUSION: 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.
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 cancerpatients. CONCLUSION: 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: J R Dev Arundhathi; Sandeep R Mathur; Ajay Gogia; S V S Deo; Purusottam Mohapatra; Chandra Prakash Prasad Journal: Mol Biol Rep Date: 2021-05-28 Impact factor: 2.316