Expression of iodine metabolism genes in human thyroid tissues: evidence for age and BRAFV600E mutation dependency.
BACKGROUND
Children present a higher susceptibility to developing thyroid cancer after radioiodine exposure and also a higher frequency of functional metastases than adults.


OBJECTIVE
To assess the mRNA expression of the sodium/iodide (Na(+)/I(-)) symporter (NIS), the Pendred syndrome gene (PDS), thyroperoxidase (TPO), thyroglobulin (Tg) and TSH receptor (TSH-R) in normal thyroid tissues (NTTs) and papillary thyroid carcinomas (PTCs) among different age groups.


METHODS
Analysis included 59 samples: 21 NTTs and 38 PTCs, of which 21 were the classic type (CPTC) and 17 the follicular variant (FVPTC). Patients were divided into three age groups: I (n = 16) 5-21 years, II (n = 13) 22-59 years, and III (n = 10) 60-91 years. The relative mRNA expression of the five target genes was determinate by quantitative reverse transcription polymerase chain reaction (QRT-PCR).


RESULTS
Expression of all genes was significantly higher in NTTs than in PTCs, and it was not age dependent in the NTT group. Among PTCs, the mean expression of PDS, TPO and TSH-R was significantly lower in group II than in group I. PDS, TPO and Tg expression was significantly lower in classic PTCs than in FVPTCs. The difference was related to a higher frequency of the BRAF(V600E) mutation in the former group.


CONCLUSIONS
The finding of higher PDS, TPO and TSH-R mRNA expression in paediatric vs. adult primary tumour tissues supports the hypothesis that this might contribute to the increased functional activity of metastases in the paediatric group. The finding that mRNA expression of the target genes in NTT was not age dependent does not provide an explanation for the higher susceptibility in the paediatric group.
Espadinha
Carla
C
Centro de Investigação de Patobiologia Molecular, Instituto Português de Oncologia de Lisboa, Lisbon, Portugal.
Santos
Jorge Rosa
JR
Sobrinho
Luís G
LG
Bugalho
Maria João
MJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000378:metabolism*; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism; D007455:Iodine / Q000378:metabolism*; D033862:Iron-Binding Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000378:metabolism*; D011989:Receptors, Thyrotropin / Q000235:genetics / Q000378:metabolism; D000076988:Sulfate Transporters; D027981:Symporters / Q000235:genetics / Q000378:metabolism; D013954:Thyroglobulin / Q000235:genetics / Q000378:metabolism; D013961:Thyroid Gland / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism; D055815:Young Adult; D000099209:Sodium-Iodide Symporters
D001324:Autoantigens; D007453:Iodide Peroxidase; D007455:Iodine; D033862:Iron-Binding Proteins; D026901:Membrane Transport Proteins; D048493:Proto-Oncogene Proteins B-raf; D011989:Receptors, Thyrotropin; D000076988:Sulfate Transporters; D027981:Symporters; D013954:Thyroglobulin; D000099209:Sodium-Iodide Symporters; C085609:SLC26A4 protein, human; C056658:TPO protein, human; C482119:BRAF protein, human