Sep 12, 2016 in this article, we focus on the molecular genetics of epithelial thyroid cancer, with an overview of the imaging features of primary and metastatic epithelial thyroid cancer. The well differentiated thyroid cancer such as follicular and papillary carcinomas account for 95% of all thyroid cancer cases and are generally associated with a good prognosis andor survival rate when diagnosed early 3, 4. Measuring molecular markers, which are gene mutations that are seen in cancer, allows the identification of indeterminate biopsies as benign and, thus, to avoid surgery. Molecular and genetic features of atc are widely heterogeneous as well and many efforts have been made to find a common profile in order to clarify its cancerogenetic process. Papillary and follicular cancers are differentiated carcinomas of thyrocytes. May, 2016 these and other emerging molecular markers may provide additional approaches to thyroid tumour classification such as suggested in the cancer genome atlas project, and may stimulate the development of novel approaches to tumour diagnosis and additional parameters for prognostic assessment as well as potential biologic therapeutic strategies. Nextgeneration sequencing molecular marker assay results. In addition to braf mutation, which has been studied most extensively, detection of ras, retptc, and pax8ppar. The most frequent type of thyroid malignancy is papillary carcinoma, which constitutes approximately 80% of all cases. Genetic diagnosis of endocrine disorders 2nd edition. We also briefly discuss the management of thyroid cancer, including novel.
The aggressiveness of thyroid tumors is closely linked to specific gene alterations. A pet scan8 can be very useful if your thyroid cancer is one that doesnt take up radioactive iodine. Department of molecular medicine, faculty of medicine, university of malaya, 50603 kuala lumpur, malaysia. This has led to a paradigm shift in the way entities are defined. Thyroid cancer is the most common type of endocrine malignancy and its incidence is steadily increasing. Differentiated thyroid cancer is the most frequent subtype of thyroid cancer and in most patients the standard treatment surgery followed by either radioactive iodine or observation is effective.
Learn more about covid19 and where to go if you have concerns. Thyroid cancer is the most common type of endocrine malignancy, with approximately 55,000 new cases diagnosed in the united states in 2012. Moleculardirected treatment of differentiated thyroid cancer. Molecular testing of fna samples advances in molecular testing may increase diagnostic accuracy of fna n engl j med, 2012. Genetic alterations and molecular biomarker investigations mardiaty iryani abdullah 1,5, sarni mat junit, khoon leong ng2, jaime jacqueline jayapalan3, barani karikalan4 and onn haji hashim1,3 1. Urging families with thyroid cancer to seek genetic testing. Download citation molecular genetics and diagnosis of thyroid cancer thyroid cancer is a common type of endocrine malignancy, and its incidence has been steadily increasing in many regions of.
Objective to summarize available data on the use of molecular. Different genetic mutations and other molecular alterations in papillary thyroid cancer ptc and follicular thyroid cancer ftc can be detected in fineneedle aspiration fna of thyroid nodules, and can be used successfully to ameliorate cancer diagnosis and management of patients with thyroid nodules. Molecular genetics and diagnostics of thyroid cancer. Papillary thyroid cancer known associated genetic mutations.
Knowledge of genetic alterations occurring in thyroid cancer has rapidly expanded in the past decade. Mutations identified in papillary thyroid cancer ptc can be subdivided into braf or raslike and include braf, retptc, ras, trk, tert, and eif1ax. However, large prospective studies are still required to evaluate the diagnostic and prognostic value of these genetic determinants in clinical. Autopsy pathological studies suggest the prevalence. Molecular pathogenesis and mechanisms of thyroid cancer. Anaplastic thyroid carcinoma atc is the most aggressive form of thyroid cancer. It is one of the few cancers whereby incidence rates have increased in recent years. Mcfadden, md, phd assistant professor department of internal medicine department of biochemistry dr. Thyroid cancer occurs in 5% to 15% of thyroid nodules detected. Rusinek d, swierniak m, chmielik e, kowal m, kowalska m, cyplinska r. Molecular genetics and diagnosis of thyroid cancer. Thyroid cancer tc is the most common endocrine malignancy with steadily increasing incidence over the past few decades. Common genetic variants in the 8q24 region and risk of papillary thyroid cancer. For the management of abnormal cervical screening tests and cancer precursors.
Molecular analysis of thyroid tumors modern pathology. Recent studies have demonstrated the feasibility of mutation detection in clinical fna samples from thyroid nodules and their. Thyroid biopsy and molecular testing for workup and diagnosis of thyroid nodules and thyroid cancer schedule an appointment coronavirus covid19 advisory. Papillary thyroid cancer genetics and special cases. However, thyroid nodules are much more prevalent, particularly with increased age, and only a small fraction of those are malignant. Wirth, md, on unmet needs in the treatment of thyroid cancer. Molecular genetics of thyroid cancer volume 98 maha reba, ahmed reba. Molecular genetics of thyroid cancer genetics research.
Molecular marker testing may be helpful in guiding patientoriented and tailored management of thyroid nodules and thyroid cancer. Ptc can occur at any age and has rarely been diagnosed as a congenital tumour. Detection of genetic alterations using molecular techniques is important for preoperative fineneedle aspiration diagnosis, prognosis and treatment of thyroid cancer. To summarize the most common commercially available molecular testing in thyroid cancer, focusing. The pathogenesis of the development and progression of thyroid cancer tc is far from being clear at present. Molecular testing is increasingly becoming the new standard of care in evaluating thyroid nodules for the presence of cancer. The analytical sensitivity, specificity, and robustness of the test have been successfully validated and indicate its suitability for clinical use. Aug 30, 2011 molecular genetics and diagnosis of thyroid cancer. Family members may have also inherited this abnormal gene. An evaluation of the molecular marker tests for thyroid cancer. On the other hand, the poorly or undifferentiated anaplastic thyroid carcinoma, albeit a rare cancer, is almost always fatal 5. Molecular genetics in the diagnosis and management of. In the united states, the average annual increase in thyroid cancer incidence of 6.
Molecular testing of thyroid fineneedle aspirations improves presurgical diagnosis and supports the histologic identification of minimally invasive follicular thyroid carcinomas. Thyroid cancer molecular profiling of thyroid nodules e. New strategies in diagnosing cancer in thyroid nodules. Analytical performance of the thyroseq v3 genomic classifier. If your doctor thinks a biopsy is needed, the simplest way to find out if a thyroid lump or nodule is cancerous is with a fine needle aspiration fna of the thyroid nodule. The method appears to be highly accurate 92% in classifying these thyroid nodules into cancer or benign. In recent years, knowledge of the genetics of differentiated thyroid carcinomas has been rapidly increasing.
Although standard strategies for the management of tc offer optimal outcomes in tc patients with favorable histological types at early stage, challenges arising from diagnosis and therapy still exist during clinical practice. Current concepts in the molecular genetics and management. We also briefly discuss the management of thyroid cancer, including novel mtt s, with emphasis on the role of imaging in assessment of treatment response and detection of. The results of this study indicate that a nextgeneration molecular marker significantly improves the diagnosis of cancer in thyroid nodules found to be a follicular neoplasm or suspicious for follicular neoplasm on thyroid biopsy. How might molecular testing advances the care of patients. Thyroid cancer is typically diagnosed after identification and evaluation of a thyroid nodule. Detection of these genetic alterations using molecular techniques is important for preoperative fineneedle aspiration diagnosis, prognosis and treatment of thyroid cancer. In her recent presentation at the 2014 annual meeting of the american head and neck society ahns, livolsi described how molecular testing for genetic alterations such asbrafandrasmutation and retptc translocation has begun to influence diagnosis with fine. It appears that molecular testing is most beneficial for thyroid fna samples with indeterminate cytology, where it can resolve the diagnosis in a significant number of cases. Biopsy the actual diagnosis of thyroid cancer is made with a biopsy, in which cells from the suspicious area are removed and looked at in the lab. There are 3 such companies offering measurement of molecular markers in thyroid biopsy specimens. Thyroid cancer and genetics thyroid cancer treatment and.
Molecular genetics in the diagnosis and management of thyroid. Preoperative diagnosis of benign thyroid nodules with indeterminate cytology. Mcfadden has disclosed no financial relationships related to the content of this. To define molecular biology in clinical practice for diagnosis, surgical management, and prognostication of differentiated thyroid cancer.
The leading genetic alterations in follicular thyroid carcinoma ftc are ras, pax8pparg, pten, pi3kakt pathway, and. Molecular genetics and diagnosis of thyroid cancer nature. Apr 30, 2020 detection of genetic alterations using molecular techniques is important for preoperative fineneedle aspiration diagnosis, prognosis and treatment of thyroid cancer. Although the death rate of thyroid cancer is relatively low, the rate of disease recurrence or persistence is high, which is associated. Thyroid cancer is the most common malignancy of endocrine organs. This methodology is now included in recommendations of leading clinical guidelines, including those from the american thyroid association ata, national comprehensive cancer network and uptodate. Molecular diagnosis of thyroid cancer sciencedirect. This chapter focuses on the molecular genetics of thyroid cancer and its clinical management.
Many of these mutations, particularly those leading to the activation of the mapk pathway, are being actively explored as therapeutic targets for thyroid cancer. Thyroid cancer is a common endocrine malignancy that has rapidly increased in global incidence in recent decades 1,2. In this study, we provide genetic characterization of locally advanced t4 well differentiated thyroid cancer and demonstrate that the majority 1925, 76% are driven by braf v600e mutation and 12. Common mutations found in thyroid cancer are point mutation of the braf and ras genes as well as retptc and pax8ppar. The knowledge of molecular genetics of thyroid cancer eventually getting the clinical impact, such as improvement of diagnostic accuracy, management of thyroid cancer, and surgical planning and can be a prognostic markers.
Papillary carcinomas frequently have genetic alterations leading to the activation of the mapk signal pathway. Ret, retptc, pten, akt1, tp53, braf, and ras among others and mutations in these genes have been implicated in thyroid carcinogenesis. Most studies are focused on dissecting its genetic basis, since our current knowledge of the genetic background of the different. Accumulated evidence suggests that it is a complex polygenic disorder for which genetic factors play an important role in disease aetiology. This multiauthor subspecialty book focuses on the diagnosis of diseases of the thyroid, with a special emphasis on the underlying molecular genetics. The actual diagnosis of thyroid cancer is made with a biopsy, in which cells from the suspicious area are removed and looked at in the lab. An overview article pdf available in international journal of surgery 411. Nsgc genetic conditions the genetics of thyroid cancer. Ret mutation is associated with lymph node metastases at diagnosis. In patients over the age of 50, feeling the neck will detect nodules in 810% of patients, and radiology tests such as ultrasound, magnetic resonance imaging mri, or computed tomography ct will detect nodules in over 50% of individuals over the age of 50. Papillary carcinoma and follicular carcinoma are the most common types of thyroid cancer and represent those tumor types for which use of molecular markers for. Thyroid cancer is a common type of endocrine malignancy, and its incidence has been steadily increasing in many regions of the world.
Molecular pathology techniques have had a dramatic effect on the diagnosis of haematological malignancies and soft tissue sarcomas. In this situation, the pet scan may be able to tell whether the cancer has spread. Therefore, the major clinical challenge is to reliably differentiate those nodules that are malignant and need to be. Thyroid cancer early detection, diagnosis, and staging. In summary, the diagnosis and treatment of thyroid cancer is nowadays influenced by the molecular characterization of thyroid cancer types. Update on the molecular diagnosis and targeted therapy of. Thyroid cancer is the most rapidly increasing cancer diagnosis in the united states, and in other countries, and is predicted to become the third most common cancer diagnosis in women with significant associated health care costs and patient morbidity seer. In this article, we focus on the molecular genetics of epithelial thyroid cancer, with an overview of the imaging features of primary and metastatic epithelial thyroid cancer. It occurs in all age groups, from children through to seniors.
The thyroid comprises two specialized cell types, follicular thyrocytes and c cells. Molecular oncology testing for cancer diagnosis, prognosis, and treatment decisions page 1 of 41 unitedhealthcare commercial medical policy effective 04012020. Thyroid cancer is one of the few types of carcinoma having such genetic. Molecular diagnosis in breast cancer sciencedirect. Molecular genetics of thyroid cancer alterations on some genes and pathways have been described to be associated with the di erent forms of thyroid cancer. Common genetic determinants of thyroid cancer subtypes. Importance thyroid cancer incidence is increasing, and when fineneedle aspiration biopsy results are cytologically indeterminate, the diagnosis is often still established only after thyroidectomy. Thyroid cancer is the fifth most common cancer in women in the usa, and an estimated over 62 000 new cases occurred in men and women in 2015. Molecular oncology testing for cancer diagnosis, prognosis.
Diagnostic pathology and molecular genetics of the thyroid. Papillary carcinoma, the most common thyroid malignancy, frequently carries braf, retptc, or ras mutations. Papillary thyroid cancer genetic abnormalities have largely been well identified following the human genome project and the cancer genome project. These genetic alterations are found in more than 70% of papillary and follicular thyroid carcinomas. Molecular oncology testing for cancer diagnosis, prognosis, and treatment decisions page 4 of 41 unitedhealthcare commercial medical policy effective 04012020 proprietary information of unitedhealthcare. Several diagnostic and prognostic molecular markers such as braf and ras. Molecular diagnostics and predictors in thyroid cancer thyroid. Although modern diagnosis methods enable the identification of tumors of small. Thyroid cancer is the most common malignant tumor of the endocrine system and accounts for approximately 1% of all newly diagnosed cancer cases. Current concepts in the molecular genetics and management of.
Genetic alterations, including braf and ras point mutations, and retptc and pax8ppar. Thyroid cancer, a cancerous tumor or growth located within the thyroid gland, is the most common endocrine cancer. Genetic diagnosis of endocrine disorders, second edition provides users with a comprehensive reference that is organized by endocrine grouping i. This diagnostic dilemma and the aforementioned prognostic difficulties justify the great expectations that were put in the molecular characterization of ptc. Molecular markers emerge in the diagnosis of thyroid cancer. If this cancer is diagnosed, the patient may have been born with a certain abnormal gene which may have led to the cancer. Thyroid nodules are exceedingly common and the incidence increases steadily with age. The essential diagnostic criteria in ptc still relies in the cytological nuclear features. Molecular genetics and the diagnosis of thyroid cancer. In summary, it is now evident that the most important driver of genetic events of papillary and follicular thyroid cancer, respectively, occur in the mapk and pi3kakt pathways. Tests have been developed to determine who has the genetic defect long before any cancer appears.
The primary purpose is to provide a comprehensive desktop reference for the diagnosis and reporting of thyroid disease, both neoplastic and nonneoplastic. Thyroid tumorigenesis and progression are closely linked to somatic point mutations. It shows a wide spectrum of morphological presentations and the diagnosis could be challenging due to its high degree of dedifferentiation. Molecular genetics in the diagnosis and management of thyroid cancer internal medicine grand rounds ut southwestern medical center april 29th, 2016 david g. The improvement of such techniques would help to reduce unnecessary treatments in indolent thyroid cancers, as well as improve the outcomes in patients with clinically aggressive cancers. It is also evident that mutations seen in thyroid cancer are almost always mutually exclusive. Early changes in the transcriptome, based on a transgenic mouse model of papillary thyroid carcinoma. Thyroid cancer is a common and mostly treatable disease, though there are some aggressive forms of thyroid cancer that do not respond to treatment. Advances in molecular testing have enabled families of those with thyroid cancers to determine whether or not they may be at increased risk for developing thyroid cancer and, if appropriate, to take preventive measures that can minimize that risk. Some molecular markers, such as braf, offer help in risk stratification and can be potentially used to optimize surgical and postsurgical management of patients with thyroid cancer.
Definition of molecular diagnosis nci dictionary of cancer. Molecular testing in the diagnosis of differentiated thyroid. Molecular diagnostics of thyroid tumors archives of pathology. Molecular approaches to thyroid cancer diagnosis in. Recent advances in molecular genetics of thyroid cancer can be applied to developing new diagnostic markers for fna samples 17, 18. Pdf molecular genetics of thyroid cancer researchgate. Molecular diagnostics and predictors in thyroid cancer. Highly accurate diagnosis of cancer in thyroid nodules with follicular neoplasmsuspicious for a follicular neoplasm cytology by thyroseq v2 nextgeneration sequencing assay. An abnormal gene has been found in patients with some forms of thyroid cancer.
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