BNIP-3 negativity was associated with capsular invasion in FC (<i>p</i> = 0.001), and p62 negativity was associated with lymph node metastasis in MC (<i>p</i> = 0.006).
As such, this article addresses the following aspects of intragenic mutations in thyroid cancer: thyroid stimulating hormone receptor and guanine-nucleotide-binding proteins of the stimulatory family mutations in hyperfunctioning tumors; mutations in RAS and other genes and aneuploidy; PAX8-PPARgamma rearrangements; BRAF mutations; mutations in oxidative phosphorylation and Krebs cycle genes in Hürthle cell tumors; mutations in succinate dehydrogenase genes in medullary carcinoma and C-cell hyperplasia; and mutations in TP53 and other genes in poorly differentiated and anaplastic carcinomas.
Genetic analysis of both tumour components showed a distinctive mutational pattern: in the MTC a Cys634Arg substitution in exon 11 of the RET gene and in the two PTC foci a Val600Glu substitution in exon 15 of the BRAF gene.
Although BRAF mutations are detected exclusively in papillary carcinoma, they are also found in medullary carcinoma and follicular carcinoma.[Corrected]
In the present work, we have investigated the effect of two serine/threonine-protein kinase B-Raf (BRAF) inhibitors (RAF265 and SB590885), and a PI3K inhibitor (ZSTK474), on RET-mediated signalling and proliferation in a MTC cell line (TT cells) harbouring the RETC634W activating mutation.
Certain mutations, such as mutations of BRAF in papillary thyroid carcinoma and mutations in RET codons 883, 918, and 928, are associated with an aggressive course in medullary thyroid carcinoma, and affected patients need close surveillance.
Direct sequencing of RET (exons 8, 10, 11, 13, 14, 15, 16), BRAF (exons 11 and 15), and KRAS, HRAS, and NRAS genes (exons 2, 3, and 4) was performed on DNA prepared from 50 MTC samples, including 30 sporadic cases.
Classical point mutations of RET, BRAF and RAS oncogenes are not shared in papillary and medullary thyroid cancer occurring simultaneously in the same gland.
In addition, MC had a higher MMRd rate (0.892, 95% CI 0.758-0.956), higher BRAF(V600E) mutation rate (0.652, 95% CI 0.143-0.954) and lower KRAS mutation rate (0.171, 95% CI 0.065-0.378) than PDA/UDA and conventional adenocarcinoma.
BRAF mutation testing plays an increasingly important role in perioperative management and has potential for targeted molecular therapies.Prophylactic thyroidectomy is indicated early in life for RET mutation carriers at risk for medullary thyroid cancer.
Glucose transporter 1 and tumoral monocarbonylate transporter 4 expression levels were shown to be the highest in anaplastic carcinoma, and medullary carcinoma showed the highest carbonic anhydrase IX and lowest hexokinase II levels compared with other subtypes.
It is suggested that this change is related to the different diagnostic approach predominant in each period of time and that MTCs discovered at a preclinical stage by calcitonin screening are equally distributed between the sexes, while females predominate when tumours have progressed until they are clinically evident.
This study was aimed to determine the time trend cure and survival rates in sporadic MTC according to the use of systematic preoperative calcitonin screening.
ISH analysis of calcitonin mRNA may therefore be a very valuable addition to ICC analysis of the peptide as a diagnostic and prognostic marker for MTC.
Compartment-oriented lymphadenectomy performed early in the course of MTC is safe and may return calcitonin levels to normal in up to 25% of carefully selected patients.
Calcitonin levels were not useful for differentiating between CCH and MTC, but in all patients with LNMs at least the stimulated calcitonin levels were assayed.
Given these case results, we suggest that screening of RET and pre-surgical Ct levels in the management of MTC patients is essential for earlier diagnosis and more normative initial treatment, that FMTC patients with cervical lymph nodes metastases may be cured by TT with MBiND, and that prophylactic VI compartmental dissection should be avoided when Ct levels are low.
Thyroidectomy was done before the age of 1 year in 20 patients, which led to long-term remission (ie, undetectable calcitonin level) in 15 (83%) of 18 individuals (2 patients died of causes unrelated to medullary thyroid carcinoma).
mRNA isolated from medullary carcinoma of the thyroid (MTC) in six patients with the inherited multiple endocrine neoplasia syndrome type 2 and cervical metastases in two patients with sporadic MTC was screened for the presence of calcitonin and proopiomelanocortin (POMC) related sequences by blot hybridization analysis.
Calcitonin is the specific serum marker; its doubling time is the most important prognostic factor for survival and progression; 30% of MTC patients have distant metastases at diagnosis and, when progressing, systemic therapy with vandetanib or cabozantinib should be considered.