Intratumoral lactate metabolism in Barrett's esophagus and adenocarcinoma.
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.


MATERIALS AND 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.
['Huhta|Heikki|H|', 'Helminen|Olli|O|', 'Palomäki|Sami|S|', 'Kauppila|Joonas H|JH|', 'Saarnio|Juha|J|', 'Lehenkari|Petri P|PP|', 'Karttunen|Tuomo J|TJ|']
D000230:Adenocarcinoma D000328:Adult D000368:Aged D000369:Aged, 80 and over D001471:Barrett Esophagus D003576:Electron Transport Complex IV D004938:Esophageal Neoplasms D005260:Female D006801:Humans D007773:Lactates D008297:Male D008875:Middle Aged D027501:Monocarboxylic Acid Transporters D009124:Muscle Proteins D016019:Survival Analysis D027981:Symporters
esophageal adenocarcinoma MCT1 MCT4 MTCO1 Barrett’s esophagus