Intratumoral lactate metabolism in Barrett’s esophagus and adenocarcinoma

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Kauppila, Joonas HKarolinska Institutet (author)

Intratumoral lactate metabolism in Barrett’s esophagus and adenocarcinoma

Article/chapterEnglish2017

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2017-02-11
Stockholm :Karolinska Institutet, Dept of Molecular Medicine and Surgery,2017
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LIBRIS-ID:oai:openarchive.ki.se:10616/45901
ISSN:1949-2553
10616/45901hdl
http://hdl.handle.net/10616/45901URI
https://doi.org/10.18632/oncotarget.15284DOI
http://kipublications.ki.se/Default.aspx?queryparsed=id:135591907URI

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Language:English
Summary in:English

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Subject category:art swepub-publicationtype

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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.

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Huhta, Heikki (author)
Helminen, Olli (author)
Palomäki, Sami (author)
Lehenkari, Petri (author)
Saarnio, Juha (author)
Karttunen, Tuomo (author)
Karolinska Institutet
Karolinska Institutet
Karolinska Institutet (creator_code:org_t)

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In:OncotargetStockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery1949-2553

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By the author/editor: Kauppila, Joonas ...; Huhta, Heikki; Helminen, Olli; Palomäki, Sami; Lehenkari, Petri; Saarnio, Juha; show more...; Karttunen, Tuomo; show less...

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