title: Intratumoral lactate metabolism in Barrett's esophagus and adenocarcinoma.
abstract: BACKGROUND
  Monocarboxylate transporters (MCTs) are cell membrane proteins which transport pyruvate, lactate and ketone bodies across the plasma membrane. MCTs are activated in various cancers, but their expression in esophageal adenocarcinoma is not known. The present study was conducted to elucidate the expression of MCTs in esophageal adenocarcinoma and its precursor lesions.
  
  
  RESULTS
  Cytoplasmic MCT1, MCT4 and MTCO1 expression linearly increased from normal epithelium to Barrett's mucosa to dysplasia and cancer. Low cytoplasmic MCT1 expression associated with high T-class (P < 0.01), positive lymph node metastases (P < 0.05), positive distant metastases (P < 0.01) and high tumor stage (P < 0.01). High cytoplasmic MCT4 expression correlated significantly with positive distant metastases (P < 0.05). Both low MCT1 and high MCT4 histoscore predicted survival in univariate analysis (P < 0.01). MCT4 histoscore predicted survival in multivariate analysis (P = 0.043; HR 1.8 95%CI 1.0-3.1). MTCO1 expression was not correlated to clinicopathological variables or survival.
  
  
  METHODS
  MCT1, MCT4 and mitochondrial cytochrome c oxidase (MTCO1) expression were determined with immunohistochemistry in esophageal specimens from 129 patients with columnar dysplasia or adenocarcinoma. Specimens including normal esophagus (n = 88), gastric (n = 67) or intestinal metaplasia (n = 51), low-grade (n = 42), high-grade dysplasia (n = 37) and esophageal adenocarcinoma (n = 99) were evaluated.
  
  
  CONCLUSIONS
  Major increase in markers of tumor metabolism occurs during carcinogenesis and progression of esophageal adenocarcinoma. MCT1 and MCT4 are prognostic factors in esophageal adenocarcinoma.
authors.affiliation: Departments of Pathology, University of Oulu, Oulu, Finland.|Departments of Surgery, University of Oulu, Oulu, Finland.|Medical Research Center Oulu, Oulu, Finland.|Oulu University Hospital, Oulu, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Huhta
authors.affiliation: Departments of Pathology, University of Oulu, Oulu, Finland.|Departments of Surgery, University of Oulu, Oulu, Finland.|Medical Research Center Oulu, Oulu, Finland.|Oulu University Hospital, Oulu, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Helminen
authors.affiliation: Medical Research Center Oulu, Oulu, Finland.|Oulu University Hospital, Oulu, Finland.
authors.forename: Sami
authors.initials: S
authors.lastname: Palomäki
authors.affiliation: Departments of Pathology, University of Oulu, Oulu, Finland.|Departments of Surgery, University of Oulu, Oulu, Finland.|Medical Research Center Oulu, Oulu, Finland.|Oulu University Hospital, Oulu, Finland.|Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Joonas H
authors.initials: JH
authors.lastname: Kauppila
authors.affiliation: Departments of Surgery, University of Oulu, Oulu, Finland.|Medical Research Center Oulu, Oulu, Finland.|Oulu University Hospital, Oulu, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Saarnio
authors.affiliation: Departments of Surgery, University of Oulu, Oulu, Finland.|Medical Research Center Oulu, Oulu, Finland.|Medical Research Center Oulu, Oulu, Finland.|Oulu University Hospital, Oulu, Finland.
authors.forename: Petri P
authors.initials: PP
authors.lastname: Lehenkari
authors.affiliation: Departments of Pathology, University of Oulu, Oulu, Finland.|Medical Research Center Oulu, Oulu, Finland.|Oulu University Hospital, Oulu, Finland.
authors.forename: Tuomo J
authors.initials: TJ
authors.lastname: Karttunen
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000378:metabolism* / Q000473:pathology; D003576:Electron Transport Complex IV; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007773:Lactates / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D016019:Survival Analysis; D027981:Symporters / Q000378:metabolism; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D003576:Electron Transport Complex IV; D007773:Lactates; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C406962:SLC16A4 protein, human; C581860:cytochrome c oxidase subunit I, human
keywords: Barrett’s esophagus; MCT1; MCT4; MTCO1; esophageal adenocarcinoma