Molecular profiling of low-risk papillary thyroid carcinoma (mPTC) on active surveillance.

Context: The active surveillance (AS) program for papillary thyroid carcinoma (≤ 1 cm) at low-risk (mPTC) showed a low percentage of progression.

Objective: The aim of this study was to find a molecular signature of cases that showed disease progression during AS, which would allow their early identification.

Methods: We performed next generation sequencing of 95 fine needle aspiration cytology specimens from cases prospectively enrolled in the AS program to analyze key somatic driver alterations or gene fusions implicated in PTC tumorigenesis.

Minor role of TP53 and TERT promoter mutations in medullary thyroid carcinoma: report of new cases and revision of the literature.

Purpose: Aims of this study were to investigate the prevalence of TP53 and TERT mutations in Medullary Thyroid carcinoma (MTC) and their role in inducing aggressiveness in positive cases.

Methods: We performed a literature search in PubMed to identify studies investigating the prevalence of TERT and TP53 mutations in MTC. We also included data on MTC cases (n = 193) obtained at our center and unpublished.

BRAF K601E Mutation in Oncocytic Carcinoma of the Thyroid: A Case Report and Literature Review.

Background: Thyroid carcinoma (TC) is the most common endocrine cancer, with papillary thyroid carcinoma (PTC) being the most common subtype. BRAF and RAS oncogene were characterized as the most frequently altered genes in PTC, with a strong association between genotype and histotype. The most common mutation in BRAF gene is V600E and is prevalent in classic and aggressive variants of PTC, while BRAF K601E mutation is the most common among the other rare BRAF mutations.

Chromosomal alterations in sporadic medullary thyroid carcinoma and correlation with outcome.

Somatic copy number alterations (SCNA) involving either a whole chromosome or just one of the arms, or even smaller parts, have been described in about 88% of human tumors. This study investigated the SCNA profile in 40 well-characterized sporadic medullary thyroid carcinomas by comparative genomic hybridization array. We found that 26/40 (65%) cases had at least one SCNA.

NF1 Gene Inactivation Acts as Tumor Driver in RET/RAS Negative Medullary Thyroid Carcinomas.

Objective: 20% of sporadic MTC has no RET/RAS somatic alterations or other known gene alterations. Aim of this study was to investigate RET/RAS negative MTC for the presence of NF1 alterations.

Methods: we studied 18 sporadic RET/RAS negative MTC cases: Next generation sequencing of tumoral and blood DNA was performed using a custom panel including the entire coding region of the NF1 gene.

Clinical Evolution of Sporadic Medullary Thyroid Carcinoma With Biochemical Incomplete Response After Initial Treatment.

Context: The clinical response after surgery is a determinant in the management of patients with medullary thyroid carcinoma (MTC). In case of excellent or structural incomplete response, the follow-up strategies are well designed. Conversely, in case of biochemical incomplete response (BiR) the management is not clearly defined.

Somatic RET Indels in Sporadic Medullary Thyroid Cancer: Prevalence and Response to Selpercatinib.

Context: Although the majority of RET alterations are single nucleotide variants (SNV), small deletions and/or insertions have been reported at variable prevalence. No information about the efficacy of RET-specific inhibitors in patients harboring RET indels has been provided.

Objective: We present an update on the prevalence of RET indels in medullary thyroid cancer (MTC) and describe the efficacy of selpercatinib in patients with advanced MTC with RET indels.

Pre- and Post-operative Circulating Tumoral DNA in Patients With Medullary Thyroid Carcinoma.

Context: Measurement of driver mutations in circulating tumoral DNA (ctDNA) obtained by liquid biopsy has been shown to be a sensitive biomarker in several human tumors.

Objective: The aim of this study was to evaluate the clinical relevance of pre- and post-operative ctDNA in sporadic medullary thyroid cancer (sMTC).

Methods: We studied pre- and post-operative ctDNA in 26 and 23 sMTC patients, respectively.

Active Surveillance in Gene Carriers Belonging to Families with Multiple Endocrine Neoplasia.

Multiple Endocrine Neoplasia 2 (MEN2) is a hereditary cancer syndrome for developing medullary thyroid cancer (MTC) due to germline mutations of gene. Subjects harboring a germline mutation without any clinical signs of MTC are defined as gene carriers (GCs), for whom guidelines propose a prophylactic thyroid surgery. We evaluate if active surveillance of GCs, pursuing early thyroid surgery, can be safely proposed and if it allows safely delaying thyroid surgery in children until adolescence/adulthood.

Higher Gene Expression Levels Do Not Represent anAlternative Activation Mechanism in Medullary Thyroid Carcinoma.

This study was designed to investigate whether (rearranged during transfection) mRNA over-expression could be considered an alternative driver event for the development of medullary thyroid carcinoma (MTC), and if different isoforms could play a role in MTC tumorigenesis. Eighty-three MTC patients, whose mutational profile was previously identified by next-generation sequencing (NGS) IONS5, were included in this study. Expression analysis was performed by the quantitative reverse transcription-polymerase chain reaction technique.

Whole Tumor Capsule Is Prognostic of Very Good Outcome in the Classical Variant of Papillary Thyroid Cancer.

Context: Tumor capsule integrity is becoming a relevant issue to predict the biological behavior of human tumors, including thyroid cancer.

Objective: This work aims to verify whether a whole tumor capsule in the classical variant of papillary thyroid carcinoma (CVPTC) could have as a predictive role of a good outcome as for follicular variant (FVPTC).

Methods: FVPTC (n = 600) and CVPTC (n = 554) cases were analyzed.

RET mutated C-cells proliferate more rapidly than non-mutated neoplastic cells.

A statistically significant higher prevalence of the RET p.Met918Thr somatic mutation, identified by direct sequencing, was previously reported in MTC > 2 cm than in smaller tumors. Aim of this study was to correlate the full RET and RAS mutation profile, identified by a Next Generation Sequencing approach, with the growth rate, proliferation and tumor size of MTC.

RET Copy Number Alteration in Medullary Thyroid Cancer Is a Rare Event Correlated with RET Somatic Mutations and High Allelic Frequency.

Copy number variations (CNV) of the gene have been described in 30% of Medullary Thyroid Cancer (MTC), but no information is available about their role in this tumor. This study was designed to clarify gene CNV prevalence and their potential role in MTC development. gene CNV were analyzed in 158 sporadic MTC cases using the ION Reporter Software (i.

Medullary thyroid cancer treated with vandetanib: predictors of a longer and durable response.

Vandetanib is an important treatment option for advanced metastatic medullary thyroid cancer. The aims of this study were to evaluate the predictors of both a longer response to vandetanib and the outcome. Medical records of 79 medullary thyroid cancer patients treated with vandetanib at our center were analysed.

Genetic Landscape of Somatic Mutations in a Large Cohort of Sporadic Medullary Thyroid Carcinomas Studied by Next-Generation Targeted Sequencing.

Sporadic Medullary Thyroid Carcinoma (sMTC) is a rare but aggressive thyroid tumor. RET and RAS genes are present in about 50%-80% of cases, but most of the remaining cases are still orphan of a genetic driver. We studied the largest series of sMTC by deep sequencing to define the mutational landscape.

Twenty-Five Years Experience on RET Genetic Screening on Hereditary MTC: An Update on The Prevalence of Germline RET Mutations.

Background: Pathogenic germline mutations affecting the proto-oncogene underlie the development of hereditary medullary thyroid carcinoma (MTC). The aims of this study were to evaluate the prevalence of germline mutations in a large series of MTC, collected over the last 25 years, and to reappraise their clinical significance.

Methods: We performed genetic screening in 2031 Italian subjects: patients who presented with sporadic (n = 1264) or hereditary (n = 117) MTC, plus 650 relatives.

Differential expression of RET isoforms in normal thyroid tissues, papillary and medullary thyroid carcinomas.

Pourposes: We investigated the expression of RET9 and RET51 isoforms in medullary (MTC), papillary (PTC) thyroid carcinoma, normal thyroid tissues, and pheochromocytoma (PHEO) to verify if these isoforms are present also in follicular thyroid cell-derived tissues, and if there is a differential expression of RET9 and RET51 in MTC.

Methods: Nineteen patients with MTC, 18 patients with PTC, 18 samples of contralateral normal thyroid tissues, and 5 cases of PHEO were included in this study. RET isoform expression was studied by real-time RT-PCR.

Clinical utility of genetic diagnosis for sporadic and hereditary medullary thyroid carcinoma.

Medullary thyroid cancer (MTC) is a rare thyroid tumor whose prevalence is 3-5% among all thyroid tumors. The pathogenesis of MTC is mainly related to germline or somatic RET activating point mutations that are causative of hereditary and sporadic cases, respectively. Hereditary MTC can occur as multiple endocrine neoplasia type 2A (MEN 2A), type 2B (MEN 2B) and familial MTC (FMTC) that differ for the association with other endocrine neoplasia.

Lung Recurrence of Papillary Thyroid Cancer Diagnosed With Antithyroglobulin Antibodies After 10 Years From Initial Treatment.

Papillary thyroid cancer (PTC) is the most common endocrine malignancy. More than 98% of patients achieve an excellent response with no evidence of clinical, biochemical, or structural disease after initial treatment. In these patients structural recurrence is rare, more frequently diagnosed in the first 5 years from initial treatment and almost invariably localized in neck lymph nodes.