University of Oulu

Hiltunen N, Rintala J, Väyrynen JP, Böhm J, Karttunen TJ, Huhta H, Helminen O. Monocarboxylate Transporters 1 and 4 and Prognosis in Small Bowel Neuroendocrine Tumors. Cancers. 2022; 14(10):2552.

Monocarboxylate transporters 1 and 4 and prognosis in small bowel neuroendocrine tumors

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Author: Hiltunen, Niko1; Rintala, Jukka1,2; Väyrynen, Juha P.1;
Organizations: 1Cancer and Translational Medicine Research Unit, Medical Research Center, Oulu University Hospital and University of Oulu, 90220 Oulu, Finland
2Surgery Research Unit, Medical Research Center, Oulu University Hospital and University of Oulu, 90220 Oulu, Finland
3Department of Pathology, Central Finland Central Hospital, 40620 Jyväskylä, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 4.8 MB)
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Language: English
Published: Multidisciplinary Digital Publishing Institute, 2022
Publish Date: 2022-09-12


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.

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Series: Cancers
ISSN: 2072-6694
ISSN-E: 2072-6694
ISSN-L: 2072-6694
Volume: 14
Issue: 10
Article number: 2552
DOI: 10.3390/cancers14102552
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Funding: This study was funded by Instrumentarium Science Foundation (O.H.), Mary and Georg C. Ehrnrooth Foundation (N.H., H.H., O.H.), The Finnish Cultural Foundation (HH), Vieno and Alli Suorsa Healthcare Foundation (H.H.) and Finnish State Research Funding (J.B., H.H., O.H.).
Copyright information: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (