Studies of oncogenes and tumor-suppressor genes in human thyroid carcinomas, and their clinical implications (original) (raw)
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Cancer medicine, 2016
BRAF V600E mutation, RET rearrangements, and RAS mutations are the common genetic alterations in differentiated thyroid carcinomas derived from follicular thyroid cells. However, the relationship between these alterations and iodine intake is still controversial. To clarify the influence of iodine intake on the occurrence of differentiated thyroid carcinomas, we performed molecular analyses for two differentiated carcinomas, papillary thyroid carcinomas (PTCs) and follicular thyroid carcinomas (FTCs), from an iodine-rich country (Japan) and an iodine-deficient country (Vietnam). We examined 120 PTCs (67 Japanese and 53 Vietnamese) and 74 FTCs (51 Japanese and 23 Vietnamese). We carried out allele-specific polymerase chain reaction (AS-PCR) for BRAF V600E, PCR and direct sequencing for RAS mutations (codon 12, 13, and 61 in NRAS, HRAS, and KRAS), and RT-PCR for RET/PTC1 and RET/PTC3. BRAF V600E was present in 55/67 (82.1%) Japanese PTCs and 44/53 (83%) Vietnamese PTCs. RET/PTC1 was i...
Annals of Otolaryngology Head and Neck Surgery Review Article, 2023
The majority of thyroid neoplasms originate from the thyroid epithelial follicular cells, while 3% to 5% of neoplasms arise from the C cells or parafollicular cells. Differentiated thyroid cancer (DTC), which derives from these follicular cells, includes papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), oncocytic cell carcinoma (formerly known as Hürthle Cell Carcinoma/OCC), poorly differentiated carcinoma (insular carcinoma), and anaplastic thyroid carcinoma (ACC/undifferentiated). These thyroid tumors comprise the majority, more than 90% of the cases, of all thyroid neoplasms. Of all these subtypes, ATC is the rarest and is characterized by its extremely poor prognosis. Likewise, poorly differentiated carcinoma is characterized by its aggressive behavior and its unfavorable prognosis. Recent advances in our comprehension of the molecular genetics of thyroid cancer have been made by identification of targetable genetic alterations in its pathogenesis. This paper will undergo an extensive review of molecular pathways that lead to the development of thyroid cancer, their implications in the diagnosis, surgical management, and adjuvant treatment.
Thyroid cancer: molecular aspects and new therapeutic strategies
Journal of thyroid research, 2012
Despite that thyroid cancer accounts for over 90% of tumors that arise from the endocrine system, these tumors barely represent 2% of solid tumors in adults. Many entities are grouped under the general term of thyroid cancer, and they differ in histological features as well as molecular and clinical behavior. Thus, the prognosis for patients with thyroid cancer ranges from a survival rate of >97% at 5 years, in the case of differentiated thyroid tumors sensitive to radioactive iodine, to a 4-month median survival for anaplastic tumors. The high vascularity in these tumors and the important role that oncogenic mutations may have in the RAS/RAF/MEK pathway and oncogenicity (as suggested by activating mutations and rearrangements of the RET gene) have led to the development of multitarget inhibitors in different histological subgroups of patients. The correct molecular characterization of patients with thyroid cancer is thought to be a key aspect for the future clinical management o...
Clinical Otolaryngology and Allied Sciences, 2003
There have been signi®cant advances in our understanding of carcinogenesis at the molecular level over the last 25 years. Oncogenes are of major interest as part of our search for knowledge surrounding the aetiology of cancer. There are several oncogenes associated with thyroid cancer. Detailed investigation of the nature and function of these tumour genes has provided important insights into both the tumour biology and the complex biochemical pathways of normal cellular functioning. Our knowledge of oncogene biology offers the hope of better diagnostic, therapeutic and prognostic modalities in our ®ght against this and other common cancers. Development of speci®c thyroid tumour markers and gene therapy is now a realistic prospect to supplement our present armamentarium of surgery and radiotherapy. This review aims to outline the pertinent information gained so far from studies of these oncogenes and provides both clinical relevance and fuel for further interest amongst the ENT thyroid community in this exciting area of research.
Thyroid Cancer: Current Molecular Perspectives
Journal of Oncology, 2010
The thyroid cancer is a rare oncological entity, representing no more than 1% of all human malignant neoplasms. Recently, it has been demonstrated a sharp increase in incidence of differentiated thyroid carcinoma, equally occurring in both sexes. So far, multiple genetic alterations have been identified in differentiated thyroid carcinoma, leading to investigate the clinical utility of genetic studies. In particular, molecular genetic approaches searching for gene mutations in the material collected by fine needle ago-biopsy may have a particular utility in small nodules and in those specimens with an indeterminate cytology. The expansion of knowledge about genetic mutations occurring in different thyroid tumors has characterized recent years, allowing the identification of a correlation between specific mutations and phenotypic characteristics of thyroid cancers, essential for their prognosis. This review will briefly report on the histological features and the new entity represented by thyroid microcarcinoma and will focus on both environmental and genetic aspects associated with the occurrence of thyroid cancer.
The Journal of Clinical Endocrinology & Metabolism, 2003
Mono-or polyclonal antibodies are now available to detect on histological sections the Na ؉ /I ؊ symporter (NIS) at the basolateral pole of the cell, the putative iodide channel (pendrin) at the apical plasma membrane, thyroperoxidase (TPO), and members of the NADPH-oxidase family, thyroid oxidase 1 and 2 (ThOXs), part of the H 2 O 2 -generating system. The aim of this study was to correlate thyroglobulin (Tg) iodination with the presence of these proteins. Tg, T 4 -containing Tg, NIS, pendrin, TPO, ThOXs, and TSH receptor (TSHr) were detected by immunohistochemistry on tissue sections of normal thyroids and various benign and malignant thyroid disorders. Tg was present in all cases. T 4 -containing Tg was found in the adenomas, except in Hurthle cell adenomas. It was never detected in carcinomas. NIS was reduced in all types of carcinomas, whereas it was detected in noncancerous tissues. Pendrin was not expressed in carcinomas, except in follicular carcinomas, where weak staining persisted. TPO expression was present in insular, follicular carcinomas and in follicular variants of papillary carcinomas, but in a reduced percentage of cells. It was below the level of detection in papillary carcinomas. The H 2 O 2 -generating system, ThOXs, was found in all carcinomas and was even increased in papillary carcinomas. Its staining was apical in normal thyroids, whereas it was cytoplasmic in carcinomas. The TSHr was expressed in all cases, but the intensity of the staining was decreased in insular carcinomas.
Genetic basis and gene therapy trials for thyroid cancer
Cancer genomics & proteomics
Gene therapy is regarded as one of the most promising novel therapeutic approaches for hopeless cases of thyroid cancer and those not responding to traditional treatment. In the last two decades, many studies have focused on the genetic factors behind the origin and the development of thyroid cancer, in order to investigate and shed more light on the molecular pathways implicated in different differentiated or undifferentiated types of thyroid tumors. We, herein, review the current data on the main genes that have been proven to (or thought to) be implicated in thyroid cancer etiology, and which are involved in several well-known signaling pathways (such as the mitogen-activated protein kinase and phosphatidylinositol-3-kinase/Akt pathways). Moreover, we review the results of the efforts made through multiple gene therapy trials, via several gene therapy approaches/strategies, on different thyroid carcinomas. Our review leads to the conclusion that future research efforts should ser...
Radio-iodine therapy in differentiated thyroid cancer: indications and procedures
Best Practice & Research Clinical Endocrinology & Metabolism, 2008
Iodide uptake across the membranes of thyroid follicular cells and cancer cells occurs through an active transport process mediated by the sodium-iodide symporter (NIS). The rat and human NIS-coding genes were cloned and identified in 1996. Evaluation of NIS gene and protein expression is critical for the management of thyroid cancer, and several approaches to increase NIS levels have been tried. Identification of the NIS gene has provided a means of expanding its role in radionuclide therapy and molecular target-specific theragnosis (therapy and diagnosis using the same molecular target). In this article, we describe the relationship between NIS expression and the thyroid carcinoma treatment using I-131 and alternative therapeutic approaches.
Molecular Markers and Thyroid Cancer
International Journal of Advanced Research, 2016
Thyroid cancer is the most common malignant tumor of the endocrine system and includes well differentiated forms, namely papillary and follicular carcinomas, and the poorly differentiated and anaplastic carcinomas that result from the transformation of thyroid follicular cells. Notably, 5-10% of all thyroid cancers are medullary thyroid cancers that arise from parafollicular or C cells. The most common genetic mutations in papillary and follicular thyroid cancers are point mutations of the BRAF or RAS genes, while the most common chromosomal alterations are RET/PTC and PAX8/PPAR rearrangements.The inherited form of medullary thyroid cancer is transmitted as an autosomal dominant trait due to a germline mutation of the RET proto-oncogene, but these mutations occur also in some sporadic cases. The most frequent initial manifestation of thyroid cancer is the appearance of a nodule. In almost all cases, these nodules are benign; in fact, less than 5% are malignant. However, some cases are misdiagnosed, and many patients are subjected to unnecessary surgery. Therefore,, therefore, it is important that patients undergo an accurate presurgery evaluation. The most reliable diagnostic test for thyroid nodules is fine needle aspiration cytology, which accurately distinguishes between a benign and malignant lesion in most cases. However, cytological discrimination between malignant and benign follicular cancer is often difficult because of poor quality samples. Here we review the various types of thyroid cancer, the associated point mutations and characteristic gene rearrangements.