Characterisation of DEHAL1 expression in thyroid pathologies.
Iodotyrosine dehalogenase 1 (DEHAL1) is a transmembrane protein involved in the recycling of iodide in the human thyroid. The aim of the present study was (I) to investigate whether DEHAL1 expression is different in differentially functioning thyroid pathologies and (II) to evaluate DEHAL1 as a possible marker of thyroid cell differentiation.



Real-time PCR for DEHAL1 and its isoform DEHAL1B was performed in a series of 105 thyroid specimens, including toxic thyroid nodules (TTN), Graves' disease (GD) thyroids, benign cold thyroid nodules (CTN), normal thyroid tissues and thyroid cancers (follicular thyroid carcinomas (FTC), papillary thyroid carcinomas (PTC), partially differentiated thyroid cancers (PDTC) and anaplastic thyroid carcinomas (ATC)). In addition, DEHAL1 protein expression was studied by immunohistochemistry in 163 benign and malignant thyroid pathologies and normal thyroids.



(I) The highest DEHAL1 mRNA levels were found in GD thyroids, while downregulation of DEHAL1 and DEHAL1B mRNA occurred in PTC and ATC (P<0.001 and <0.05 respectively); (II) DEHAL1 protein was overexpressed in TTNs and GD thyroids with predominant apical staining in all samples; (III) a weaker and patchy staining pattern was found in CTNs and normal thyroids; (IV) in differentiated thyroid cancers (FTC and PTC), a diffuse cytoplasmic DEHAL1 expression was found; and (V) in PDTC and ATC, DEHAL1 expression was faint or absent.



Upregulation of DEHAL1 protein expression and sublocalisation of DEHAL1 at the apical cell pole in TTNs and GD thyroids is consistent with increased thyroid hormone turnover during thyrotoxicosis. Diffuse cytoplasmatic localisation or downregulation of DEHAL1 expression in thyroid cancers suggests alteration or loss of DEHAL1 function during thyroid cell dedifferentiation.
Krause
Kerstin
K
III. Medical Department, University of Leipzig, Ph.-Rosenthal-Str. 27, 04103 Leipzig, Germany.
Karger
Stefan
S
Gimm
Oliver
O
Sheu
Sien-Yi
SY
Dralle
Henning
H
Tannapfel
Andrea
A
Schmid
Kurt Werner
KW
Dupuy
Corinne
C
Fuhrer
Dagmar
D
0000-0003-0357-4192
D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006867:Hydrolases / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013959:Thyroid Diseases / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D013961:Thyroid Gland / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D013964:Thyroid Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*
D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D006867:Hydrolases; C497447:IYD protein, human