Monocarboxylate Transporters 1 and 4 and Prognosis in Small Bowel Neuroendocrine Tumors

Abstract

Monocarboxylate transporters (MCTs) are cell membrane proteins transporting lactate, pyruvate, and ketone bodies across the plasma membrane. The prognostic role of MCTs in neuroendocrine tumors is unknown. We aimed to analyze MCT1 and MCT4 expression in small bowel neuroendocrine tumors (SB-NETs). The cohort included 109 SB-NETs and 61 SB-NET lymph node metastases from two Finnish hospitals. Tumor samples were immunohistochemically stained with MCT1 and MCT4 monoclonal antibodies. The staining intensity, percentage of positive cells, and stromal staining were assessed. MCT1 and MCT4 scores (0, 1 or 2) were composed based on the staining intensity and the percentage of positive cells. Survival analyses were performed with the Kaplan–Meier method and Cox regression, adjusted for confounders. The primary outcome was disease-specific survival (DSS). A high MCT4 intensity in SB-NETs was associated with better DSS when compared to low intensity (85.7 vs. 56.6%, p = 0.020). A high MCT4 percentage of positive cells resulted in better DSS when compared to a low percentage (77.4 vs. 49.1%, p = 0.059). MCT4 scores 0, 1, and 2 showed DSS of 52.8 vs. 58.8 vs. 100% (p = 0.025), respectively. After adjusting for confounders, the mortality hazard was lowest in the patients with a high MCT4 score. MCT1 showed no association with survival. According to our study, a high MCT4 expression is associated with an improved prognosis in SB-NETs.

Keywords

• MCT1
• MCT4
• monocarboxylate transporter
• lactate
• neuroendocrine tumor
• small bowel neuroendocrine tumor