Abstract
BackgroundEndometrial 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.MethodsMCT1, MCT4 and CD147 expression was examined using immunohistochemical analysis in 90 endometrial tumours and correlated with clinico-pathological characteristics and survival outcomes.ResultsMCT1 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).ConclusionOur 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.
Highlights
Endometrial cancer (EC) is a major health concern due to its rising incidence
MCT1, MCT4 and CD147 expression, distribution and subcellular localization in EC In this study, immunohistochemical evaluation of MCT1, MCT4 and CD147 was performed in 90 EC (47 endometrioid [Endometrioid endometrial cancer (EEC)] and 43 non-endometrioid [non-EEC]) tumours
MCT1 was generally observed in peripheral zones (Fig. 2a) whereas MCT4 was expressed in central zones of the same tumour (Fig. 2b)
Summary
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. In 2012, it is estimated that more than 30,000 new diagnoses of endometrial cancer (EC) were made worldwide. In the UK, EC is the fourth most common cancer in women, with more than 9000 new cases diagnosed in 2013 [1]. EC usually presents at an early stage following the onset of postmenopausal bleeding and is generally cured by hysterectomy and bilateral salpingooophorectomy. Clinical and epidemiological studies have shown that women with obesity and type II diabetes have an increased risk of EC [5,6,7].
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