BRAFV600E mutation, but not RET/PTC rearrangements, is correlated with a lower expression of both thyroperoxidase and sodium iodide symporter genes in papillary thyroid cancer
Open accessAbstract
A low sodium iodide symporter (NIS) expression has been shown in papillary thyroid carcinomas (PTCs) harboring the BRAFV600E mutation. In the present study, we analyzed the mRNA expression of thyroid differentiation genes, glucose transporter (GLUT)-1 and GLUT-3, in 78 PTCs according to the presence of BRAFV600E or RET/PTC rearrangements. We found BRAFV600E and RET/PTC rearrangements in 35.8 and 19.4% of PTCs respectively. The mRNA expression of NIS and thyroperoxidase (TPO) genes were significantly lower (P<0.0001 and P=0.004 respectively) in BRAFV600E-positive PTC with respect to non-mutated samples. In support of this result, immunohistochemistry showed that the percentage of NIS-positive cells was significantly lower (P=0.005) in BRAFV600E-mutated PTC (mean 53.5%) than in negative cases (mean 72.6%). In contrast, no difference either in NIS or in any other thyroid differentiation genes' mRNA expression was found in PTC with or without RET/PTC rearrangements. When GLUT-1 and GLUT-3 mRNA expression was considered, no correlation was found either in BRAFV600E- nor in RET/PTC-mutated cases. In conclusion, this study confirmed the presence of a genetic alteration of BRAF and/or RET oncogenes in 64% of PTC cases and revealed a significant correlation of BRAFV600E mutation with a lower expression of both NIS and TPO. This latter finding could indicate that an early dedifferentiation process is present at the molecular level in BRAFV600E-mutated PTC, thus suggesting that the previously demonstrated poor prognostic significance of BRAFV600E mutation could be related to the dedifferentiation process more than to a more advanced stage at diagnosis.
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Dedifferentiation and development of radioactive iodine refractory diseases, resulting from decreased thyroid differentiation factors especially NIS, is a leading cause for BRAFV600E-related poor prognosis and mortality in thyroid tumorigenesis.
“Dedifferentiation and development of radioactive iodine (RAI) refractory diseases, resulted from decreased thyroid differentiation factors, especially sodium iodide symporter (NIS), is also the leading cause for BRAFV600E-related poor prognosis and mortality in thyroid tumorigenesis28–30.”
From Proteostatic reactivation of the developmental transcription factor TBX3 drives BRAF/MAPK-mediated tumorigenesis (2024) · cites this paper as [29]
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- Authors
- Romei, C., Ciampi, R., Faviana, P., Agate, L., Molinaro, E., Bottici, V., Basolo, F., Miccoli, P., Pacini, F., Pinchera, A., & Elisei, R.
- Affiliations
- University of Pisa (IT)
- University of Siena (IT)
- Venue
- Endocrine Related Cancer
- Publisher
- Bioscientifica
- Published
- 2008-06-01
- Volume
- 15
- Issue
- 2
- Pages
- 511-520
- ISSN
- 1351-0088 (ISSN-L)
- 1479-6821
- OpenAlex
- W2111349551
- Cited by
- 160
- References
- 0
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 6 · 2021: 11 · 2020: 7 · 2019: 9 · 2018: 8 · 2017: 9 · 2016: 12 · 2015: 17 · 2014: 7 · 2013: 6 · 2012: 10
- FWCI
- 11.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Endocrine Related Cancer (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- Funders
- Associazione Italiana per la Ricerca sul Cancro
- Università di Pisa
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Keywords
- papillary thyroid carcinoma, BRAF V600E mutation, RET/PTC rearrangement, sodium iodide symporter, thyroid peroxidase, GLUT1, GLUT3, tumor dedifferentiation, prognostic value
- MeSH terms
- Sodium-Iodide Symporters, Adult, Autoantigens, Carcinoma, Papillary, Cell Differentiation, Female, Humans, Immunohistochemistry, Iodide Peroxidase, Male, RNA, Messenger, Thyroid Neoplasms, Thyrotropin, Gene Rearrangement, Gene Expression Regulation, Neoplastic, Point Mutation, Symporters, Iron-Binding Proteins, Proto-Oncogene Proteins B-raf, Proto-Oncogene Proteins c-ret, Glucose Transporter Type 1, Glucose Transporter Type 3
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