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- Kauppila, Joonas H, et al.
(författare)
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Intratumoral lactate metabolism in Barrett’s esophagus and adenocarcinoma
- 2017
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Ingår i: Oncotarget. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 1949-2553.
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Tidskriftsartikel (refereegranskat)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. 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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| 2. |
- Kauppila, Joonas H, et al.
(författare)
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Tenascin-C and fibronectin in normal esophageal mucosa, Barrett's esophagus, dysplasia and adenocarcinoma
- 2017
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Ingår i: Oncotarget. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 1949-2553.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Tenascin-C and fibronectin are adhesive glycoproteins modulating the structure of the extracellular matrix and cellular functions. Their expression and function in esophageal adenocarcinoma is poorly known. The aim of this study was to evaluate the expression of tenascin-C and fibronectin in esophageal adenocarcinoma and its precursor stages. RESULTS: Stromal tenascin-C and fibronectin expression were found in all evaluated lesion types. Expression of both molecules increased from gastric metaplasia towards adenocarcinoma (p<0.05). In carcinomas, tenascin-C expression in the bulk was associated with T-stage (p=0.006), presence of lymph node (p=0.004) and distant organ metastases (p=0.007). Abundant tenascin-C expression associated with poor survival (p=0.034) in univariate analysis. Fibronectin expression associated to T-stage (p=0.030). Expression of tenascin-C or fibronectin in the tumor invasive front was not associated to clinicopathological variables or survival. No significant correlation with tumor/stroma percentage, cancer-associated fibroblasts or mean vascular density was observed with either tenascin-C or fibronectin. METHODS: Tenascin-C and fibronectin were stained immunohistochemically and assessed in esophageal specimens from patients with esophageal adenocarcinoma (n=90) or dysplasia (n=30). Structures and lesion were evaluated including normal esophagus (n=77), gastric (n=61) or intestinal (n=51) metaplasia without dysplasia, and low-grade (n=42) or high-grade (n=34) dysplasia, and esophageal adenocarcinoma (n=90). In carcinomas, both bulk and invasive front were separately evaluated. In addition, tumor/stroma percentage, cancer-associated fibroblasts and mean vascular density were evaluated. CONCLUSIONS: Tenascin-C and fibronectin are upregulated in esophageal adenocarcinoma when compared to Barrett's esophagus and dysplasia. Increased tenascin-C expression is associated with metastasis and poor prognosis in esophageal adenocarcinoma.
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