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Biochem Biophys Res Commun. 2014 Aug 15;451(1):54-61. doi: 10.1016/j.bbrc.2014.07.050. Epub 2014 Jul 21.

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

Author information

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.

KEYWORDS:

Glycolysis; Hypoxia; MCT4; Monocarboxylate transporters; Triple negative breast cancer

PMID:
25058459
DOI:
10.1016/j.bbrc.2014.07.050
[Indexed for MEDLINE]

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