BRAF V600E and decreased NIS and TPO expression are associated with aggressiveness of a subgroup of papillary thyroid microcarcinoma

© 2015 European Society of Endocrinology..

BACKGROUND: Thyroid cancer incidence has dramatically increased worldwide over the last two decades. The rise is mostly due to an increased detection of small papillary thyroid carcinomas (PTCs) (≤20  mm), predominantly microPTC (≤10  mm). Although small tumors generally have an excellent outcome, a considerable percentage may have a more aggressive disease and worse prognosis. The clinical challenge is to preoperatively identify those tumors that are more likely to recur.

AIM: To improve risk stratification and patient management, we sought to determine the prognostic value of BRAF V600E, NRAS or RET/PTC mutations in patients with PTC measuring <20  mm, mainly microPTC.

METHODS: The prevalence of RET/PTC fusion genes was examined by quantitative RT-PCR. BRAF V600E and NRAS Q61 mutations were determined by PCR sequencing. To further elucidate why some small PTC are less responsive to radioactive iodine treatment therapy, we explored if these genetic alterations may modulate the expression of iodine metabolism genes (NIS, TPO, TG, TSHR and PDS) and correlated with clinico-pathological findings that are predictors of recurrence.

RESULTS: This study shows that tumors measuring ≤20  mm exhibited higher prevalence of BRAF V600E mutation, which correlated with aggressive histopathological parameters, higher risk of recurrence, and lower expression of NIS and TPO. Although this correlation was not found when microPTC were evaluated, we show that tumors measuring 7-10  mm, which were positive for BRAF mutation, presented more aggressive features and lower expression of NIS and TPO.

CONCLUSION: We believe that our findings will help to decide the realistic usefulness of BRAF V600E mutation as a preoperative marker of poor prognosis in small PTC, primarily in microPTC.

Medienart:

E-Artikel

Erscheinungsjahr:

2015

Erschienen:

2015

Enthalten in:

Zur Gesamtaufnahme - volume:173

Enthalten in:

European journal of endocrinology - 173(2015), 4 vom: 04. Okt., Seite 525-40

Sprache:

Englisch

Beteiligte Personen:

Bastos, André Uchimura [VerfasserIn]
Oler, Gisele [VerfasserIn]
Nozima, Bruno Heidi Nakano [VerfasserIn]
Moysés, Raquel Ajub [VerfasserIn]
Cerutti, Janete Maria [VerfasserIn]

Links:

Volltext

Themen:

4XE5NDT4K1
9010-34-8
9679TC07X4
Autoantigens
BRAF protein, human
EC 1.11.1.7
EC 1.11.1.8
EC 2.7.10.1
EC 2.7.11.1
EC 3.6.1.-
GTP Phosphohydrolases
Iodide Peroxidase
Iodine
Iron-Binding Proteins
Journal Article
Membrane Proteins
Membrane Transport Proteins
NRAS protein, human
Oncogene Proteins, Fusion
Protein-Tyrosine Kinases
Proto-Oncogene Proteins B-raf
Receptors, Thyrotropin
Research Support, Non-U.S. Gov't
Ret-PTC fusion oncoproteins, human
SLC26A4 protein, human
Sodium-iodide symporter
Sulfate Transporters
Symporters
TPO protein, human
Thyroglobulin

Anmerkungen:

Date Completed 16.11.2015

Date Revised 08.04.2022

published: Print

Citation Status MEDLINE

doi:

10.1530/EJE-15-0254

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM252446801