title: The expression of monocarboxylate transporters in thyroid carcinoma can be associated with the morphological features of BRAFV600Emutation.
abstract: BRAFV600Emutation, 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 BRAFV600Eon 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 BRAFV600Emutational 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 BRAFV600Emutated papillary thyroid carcinomas suggesting the possible involvement of lactate in the morphological features.
authors.affiliation: Division of Anatomic Pathology, Catholic University of Sacred Heart-Rome, Milano, Italy. esther.rossi@rm.unicatt.it.
authors.forename: Esther Diana
authors.initials: ED
authors.lastname: Rossi
authors.affiliation: Division of Anatomic Pathology, Catholic University of Sacred Heart-Rome, Milano, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Bizzarro
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.|ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Sara
authors.initials: S
authors.lastname: Granja
authors.affiliation: Division of Anatomic Pathology, Catholic University of Sacred Heart-Rome, Milano, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Martini
authors.affiliation: Division of Anatomic Pathology, Catholic University of Sacred Heart-Rome, Milano, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Capodimonti
authors.affiliation: Division of Anatomic Pathology, Catholic University of Sacred Heart-Rome, Milano, Italy.
authors.forename: Emilia
authors.initials: E
authors.lastname: Luca
authors.affiliation: Division of Anatomic Pathology, Catholic University of Sacred Heart-Rome, Milano, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Fadda
authors.affiliation: Division of Endocrine surgery, Catholic University-Rome, Milano, Italy.
authors.forename: Celestino Pio
authors.initials: CP
authors.lastname: Lombardi
authors.affiliation: Division of Endocrinology Catholic University-Rome, Milano, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Pontecorvi
authors.affiliation: Division of Anatomic Pathology, Catholic University of Sacred Heart-Rome, Milano, Italy.
authors.forename: Luigi Maria
authors.initials: LM
authors.lastname: Larocca
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.|ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Fatima
authors.initials: F
authors.lastname: Baltazar
authors.affiliation: Medical Faculty/University, Porto, Portugal.|Institute of Pathology/Molecular Immunology of Porto, Porto, Portugal.|Laboratorie National de Sante-Luxembourg, Luxembourg, Luxembourg.
authors.forename: Fernando
authors.initials: F
authors.lastname: Schmitt
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D044963:Biopsy, Fine-Needle; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D027501:Monocarboxylic Acid Transporters / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000378:metabolism; D013961:Thyroid Gland / Q000378:metabolism / Q000473:pathology; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D027501:Monocarboxylic Acid Transporters; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF V600E mutation; Liquid-based cytology; MCTs; PTC; Plump cells; Thyroid lesions