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TitleThe expression of monocarboxylate transporters in thyroid carcinoma can be associated with the morphological features of BRAF (V600E) mutation
Author(s)Rossi, Esther Diana
Bizzarro, Tommaso
Granja, Sara Costa
Martini, Maurizio
Capodimonti, Sara
Luca, Emilia
Fadda, Guido
Lombardi, Celestino Pio
Pontecorvi, Alfredo
Baltazar, Fátima
et. al.
KeywordsLiquid-based cytology
Thyroid lesions
PTC Plump cells
BRAFV600E mutation
Plump cells
BRAF mutation V600E
Issue date10-May-2017
CitationRossi, E. D., Bizzarro, T., Granja, S., Martini, M., et. al. (2017). The expression of monocarboxylate transporters in thyroid carcinoma can be associated with the morphological features of BRAFV600E mutation. Endocrine, 56(2), 379-387
Abstract(s)BRAF (V600E) mutation, usually performed by DNA techniques, is one of the most common diagnostic markers in papillary thyroid carcinoma. Few papers have demonstrated that plump cells (eosinophilic cytoplasms and papillary thyroid carcinoma nuclei) and peculiar sickle-shaped nuclei represent morphological features of BRAF (V600E) on papillary thyroid carcinomas. These features seem to be linked to glycolytic phenotype whereby monocarboxylate transporters 1-4 are hypothesized to have a dominant role as lactate transporters. We investigated the association between these morphological features and monocarboxylate transporters 1 and 4 in 48 cyto-histological samples diagnosed as "positive for malignancy-favoring papillary thyroid carcinoma". These cases were processed with liquid-based cytology and underwent BRAF (V600E) mutational analysis (pyrosequencing) on liquid-based cytology and monocarboxylate transporters immunostaining on histology. The expression of monocarboxylate transporter 1, monocarboxylate transporter 4, glucose trasporter-1 and carbonic anhidrase were scored semi-quantitatively with expression from 0 to 3+ (strong positivity). The 33 mutated and 15 wild type cases showed 100 % cyto-histological concordance. The cytological evaluation revealed plump cells and sickle nuclear shape in 100 % mutated cases. Monocarboxylate transporter 1 yielded 76 % positivity in the mutated cases especially in both the plump cells and sickle-shaped nuclei, whereas the wild types showed 13.3 % positive monocarboxylate transporter 1 (p = 0.00013). Monocarboxylate transporter 4 resulted in 100 % positivity in mutated and 40 % in wild types (p < 0.005). Furthermore, 20 % of the wild types showed weak monocarboxylate transporter 1 nuclear expression associated to a less aggressive behavior. The analysis of glucose trasporter-1 and carbonic anhidrase did not highlight any statistical significance (p > 0.05). This is the first report analyzing the association between monocarboxylate transporter expression and the morphological features of BRAF (V600E) mutated papillary thyroid carcinomas suggesting the possible involvement of lactate in the morphological features.
Publisher version
AccessOpen access
Appears in Collections:ICVS - Artigos em revistas internacionais / Papers in international journals

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