MCT1 in Invasive Ductal Carcinoma: Monocarboxylate Metabolism and Aggressive Breast Cancer

• Published in: Frontiers in cell and developmental biology 2017-04, Vol.5, p.27-27
• Main Authors: Johnson, Jennifer M, Cotzia, Paolo, Fratamico, Roberto, Mikkilineni, Lekha, Chen, Jason, Colombo, Daniele, Mollaee, Mehri, Whitaker-Menezes, Diana, Domingo-Vidal, Marina, Lin, Zhao, Zhan, Tingting, Tuluc, Madalina, Palazzo, Juan, Birbe, Ruth C, Martinez-Outschoorn, Ubaldo E
• Format: Article
• Language: English
• Subjects: Cell and Developmental Biology
• ISSN: 2296-634X; 2296-634X
• DOI: 10.3389/fcell.2017.00027

Monocarboxylate transporter 1 (MCT1) is an importer of monocarboxylates such as lactate and pyruvate and a marker of mitochondrial metabolism. MCT1 is highly expressed in a subgroup of cancer cells to allow for catabolite uptake from the tumor microenvironment to support mitochondrial metabolism. We studied the protein expression of MCT1 in a broad group of breast invasive ductal carcinoma specimens to determine its association with breast cancer subtypes and outcomes. MCT1 expression was evaluated by immunohistochemistry on tissue micro-arrays (TMA) obtained through our tumor bank. Two hundred and fifty-seven cases were analyzed: 180 cases were estrogen receptor and/or progesterone receptor positive (ER+ and/or PR+), 62 cases were human epidermal growth factor receptor 2 positive (HER2+), and 56 cases were triple negative breast cancers (TNBC). MCT1 expression was quantified by digital pathology with Aperio software. The intensity of the staining was measured on a continuous scale (0-black to 255-bright white) using a co-localization algorithm. Statistical analysis was performed using a linear mixed model. High MCT1 expression was more commonly found in TNBC compared to ER+ and/or PR+ and compared to HER-2+ ( < 0.001). Tumors with an component were less likely to stain strongly for MCT1 ( < 0.05). High nuclear grade was associated with higher MCT1 staining ( < 0.01). Higher T stage tumors were noted to have a higher expression of MCT1 ( < 0.05). High MCT1 staining in cancer cells was associated with shorter progression free survival, increased risk of recurrence, and larger size independent of TNBC status ( < 0.05). MCT1 expression, which is a marker of high catabolite uptake and mitochondrial metabolism, is associated with recurrence in breast invasive ductal carcinoma. MCT1 expression as quantified with digital image analysis may be useful as a prognostic biomarker and to design clinical trials using MCT1 inhibitors.