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BMC Clin Pathol. 2017 Dec 28;17:27. doi: 10.1186/s12907-017-0067-7. eCollection 2017.

Monocarboxylate Transporter 1 (MCT1) is an independent prognostic biomarker in endometrial cancer.

Author information

1
Division of Pharmacy and Optometry, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
2
Gynaecological Oncology Research Group, Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Level 5 - Research, St Mary's Hospital, Oxford Road, Manchester, M13 9WL UK.
3
Department of Histopathology, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
4
Division of Population Health, Health Services Research and Primary Care, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
5
Department of Obstetrics and Gynaecology, St Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.

Abstract

Background:

Endometrial cancer (EC) is a major health concern due to its rising incidence. Whilst early stage disease is generally cured by surgery, advanced EC has a poor prognosis with limited treatment options. Altered energy metabolism is a hallmark of malignancy. Cancer cells drive tumour growth through aerobic glycolysis and must export lactate to maintain intracellular pH. The aim of this study was to evaluate the expression of the lactate/proton monocarboxylate transporters MCT1 and MCT4 and their chaperone CD147 in EC, with the ultimate aim of directing future drug development.

Methods:

MCT1, MCT4 and CD147 expression was examined using immunohistochemical analysis in 90 endometrial tumours and correlated with clinico-pathological characteristics and survival outcomes.

Results:

MCT1 and MCT4 expression was observed in the cytoplasm, the plasma membrane or both locations. CD147 was detected in the plasma membrane and associated with MCT1 (p = 0.003) but not with MCT4 (p = 0.207) expression. High MCT1 expression was associated with reduced overall survival (p = 0.029) and remained statistically significant after adjustment for survival covariates (p = 0.017).

Conclusion:

Our data suggest that MCT1 expression is an important marker of poor prognosis in EC. MCT1 inhibition may have potential as a treatment for advanced or recurrent EC.

KEYWORDS:

Endometrial cancer; Glycolysis; Hypoxia; Monocarboxylate transporters

Conflict of interest statement

The study was approved by the National Research Ethics Service Committee London - Fulham (reference 12/LO/0364). All participants gave written, informed consent to donate their tissues and clinical data for research.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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