Association of Low Sodium-Iodide Symporter Messenger Ribonucleic Acid Expression in Malignant Thyroid Nodules with Increased Intracellular Protein Staining

Objective: To extend the molecular analysis of the IVS30+1G>T intronic thyroglobulin (TG) mutation, and to report the eleven year follow-up of the affected patients. Methods: Two siblings with severe congenital hypothyroidism with fetal and neonatal goiter, harboring the IVS30+1G>T mutation were included. Nodular and non-nodular thyroid tissue specimens were collected. Specifi c thyroid genes expression was evaluated by real-timePCR and by immunohistochemistry. Results: In non-nodular tissue specifi c thyroid genes mRNA were reduced when compared to normal thyroid sample. In the nodule, TPO and NIS expression was very low. Microscopic examinations showed very large follicular-lumina and swollen vesicles of endoplasmatic-reticulum. Strong cytoplasmatic and low follicular-lumen TG immunostaining were detected. Intracellular NIS, membrane TPO and TSHR immunostaining had higher positivity in nonnodular sample. Both patients had a long-term adequate developmental outcome, besides one patient have been lately-treated. Conclusions: IVS30+1G>T mutation not only lead to very enlarge endoplasmatic-reticulum, but also to alterations of specifi c thyroid genes expression. The clinical evolution of patients harboring these mutations strengthen the concept of the infl uence of environment, like iodine nutrition, to determine the fi nal phenotypic appearance. RESUMO Análise Molecular e Acompanhamento a Longo Prazo de Dois Irmãos com Hipotireoidismo Congênito Portadores da Mutação Intrônica IVS30+1G>T noGene da Tireoglobulina. Objetivo: Aprofundar a análise molecular da mutação intrônica IVS30+1G>T do gene tireoglobulina (TG) e relatar a clínica de pacientes portadores da mutação, acompanhados por 11 anos. Métodos: Foram estudados dois irmãos com hipotireoidismo congênito grave com bócio fetal e bócio neonatal, portadores da mutação IVS30+1G>T. Foram coletadas amostras de tecido nodular e não-nodular. Avaliou-se a expressão de genes específi cos da tireóide por PCR em tempo real e imunohistoquímica. Resultados: A expressão de genes específi -cos da tireóide foi menor no tecido não-nodular que no tecido normal controle. Expressões de TPO e NIS foram extremamente baixas no tecido nodular. Verifi cou-se lúmen folicular aumentado com grandes vesículas de retículo endoplasmático, e detectou-se forte marcação de TG no citoplasma e fraca no lúmen folicular. No tecido não-nodular observou-se forte positividade de NIS intracelular e, TPO e TSHR na membrana plasmática. O acompanhamento em longo prazo dos pacientes mostrou adequado desenvolvimento, apesar de um deles ter recebido tratamento tardio. Conclusões: A mutação IVS30+1G>T não só promove alterações no retículo endoplasmático, como alterações na expressão de genes específi cos da tireóide. A evolução clínica destes pacientes reforça o conceito da infl uência do meio ambiente, como o aporte nutricional de iodo, no fenótipo fi nal.

show abstract

“…Previous reports have shown predominantly intracellular localization of NIS protein in thyroid tumors (30)(31)(32).…”

Section: Discussionmentioning

confidence: 87%

A molecular analysis and long-term follow-up of two siblings with severe congenital hypothyroidism carrying the IVS30+1G>T intronic thyroglobulin mutation

Rubio

Galrão

Pardo

et al. 2008

Arq Bras Endocrinol Metab

Self Cite

View full text Add to dashboard Cite

show abstract

“…NIS expression was localized in the lumen side of the seminiferous ducts and Leydig cells but not observed in Sertoli cells with immunohistochemical examination (6). Interestingly, Sodré et al (13) reported low NIS mRNA levels in malignant thyroid nodules, and also it was expressed intracellularly. The weak expression of NIS mRNA in testicular tissue may be reason of less concentrated radioiodine.…”

Section: Discussionmentioning

confidence: 97%

Sodium Iodide Symporter Protein Expression and Clinicopathological Variables in Pure Testicular Seminomas

Yazgan¹,

Ener²,

Gözalan³

et al. 2017

Cyprus J Med Sci

View full text Add to dashboard Cite

BACKGROUNDTestis carcinomas cause cancer-related morbidity and mortality in adults. Radioiodine I-131 (RAI) therapy may be an alternative for the treatment. The aim of this study is to investigate the presence and localization of sodium iodide symporter (NIS) expression in pure testicular seminomas, two lymph nodes with seminoma metastasis, and two embryonal carcinomas by immunohistochemically methods. MATERIAL and METHODSThe localization of NIS expression was defined as positive according to >10% membranous staining. Cytoplasmic staining was noted as present/absent. NIS expression was compared to the invasions. RESULTSThere was no rete testis invasion in 66.7% (26/37) and epididymis invasion in 84.6% (33/37) of the cases. Lymphovascular invasion was seen in 64.1% (25/37) of the cases. There was no membranous staining in pure seminomas, but it was present in two embryonal carcinomas. Cytoplasmic staining was present in 41% (16/34) of the tumors. Cytoplasmic NIS expression was present in 72.7% (p=0.135) and 75% (p=0.6) of the rete testis and epididymis invasions, respectively. There was no statistically important relationship with the cytoplasmic expression, lymphovascular invasion, and the other parameters (p>0.05). CONCLUSIONResearch of NIS expression in pure seminomas with larger series may clear the option of RAI treatment in seminomas. Also, evidence of different expression profiles in non-seminomatous testicular tumors was determined.

show abstract

“…Reduced TSH-R may also cause low NIS mRNA levels and deficient NIS migration (Sodre et al, 2008). Activation of BRAF, Ras and RET decrease NIS mRNA.…”

Section: Nis In Thyroid Cancermentioning

confidence: 99%

Differentiation Therapy in Thyroid Carcinoma

Frőhlich¹,

Wahl²

2012

Updates in the Understanding and Management of Thyroid Cancer

View full text Add to dashboard Cite

Association of Low Sodium-Iodide Symporter Messenger Ribonucleic Acid Expression in Malignant Thyroid Nodules with Increased Intracellular Protein Staining

Cited by 39 publications

References 15 publications

A molecular analysis and long-term follow-up of two siblings with severe congenital hypothyroidism carrying the IVS30+1G>T intronic thyroglobulin mutation

A molecular analysis and long-term follow-up of two siblings with severe congenital hypothyroidism carrying the IVS30+1G>T intronic thyroglobulin mutation

Sodium Iodide Symporter Protein Expression and Clinicopathological Variables in Pure Testicular Seminomas

Differentiation Therapy in Thyroid Carcinoma

Contact Info

Product

Resources

About