TY - JOUR
T1 - Molecular pathology of hereditary and sporadic medullary thyroid carcinomas
AU - Chernock, Rebecca D.
AU - Hagemann, Ian S.
N1 - Publisher Copyright:
© American Society for Clinical Pathology.
Copyright:
Copyright 2015 Elsevier B.V., All rights reserved.
PY - 2015/6
Y1 - 2015/6
N2 - Objectives: Medullary thyroid carcinoma (MTC) is a relatively uncommon type of thyroid malignancy, with unique histologic features and molecular pathology. It is important to recognize, because its management, which is in part driven by the genetic basis of this disease, is different from follicular-derived thyroid tumors. The aim of this article is to briefly review the histopathologic features of MTC and then explore its molecular pathology, including the role of molecular diagnostic testing and the use of targeted therapy for advanced disease. Methods: A review of published literature was performed. Results: A subset of MTC cases is hereditary and due to germline mutations in the RET tyrosine kinase receptor gene. Somatic mutations in either RET or RAS are also present in most sporadic tumors. Conclusions: Molecular genetic testing is routinely performed to identify hereditary cases. In addition, understanding the molecular basis of both hereditary and sporadic MTC has led to the development of targeted therapy with tyrosine kinase inhibitors. Although additional data are needed, tumor mutation status may affect response to targeted therapy. Therefore, it is possible that genetic testing of tumor tissue to predict treatment response, as is currently done for other cancer types, may come into practice in the future.
AB - Objectives: Medullary thyroid carcinoma (MTC) is a relatively uncommon type of thyroid malignancy, with unique histologic features and molecular pathology. It is important to recognize, because its management, which is in part driven by the genetic basis of this disease, is different from follicular-derived thyroid tumors. The aim of this article is to briefly review the histopathologic features of MTC and then explore its molecular pathology, including the role of molecular diagnostic testing and the use of targeted therapy for advanced disease. Methods: A review of published literature was performed. Results: A subset of MTC cases is hereditary and due to germline mutations in the RET tyrosine kinase receptor gene. Somatic mutations in either RET or RAS are also present in most sporadic tumors. Conclusions: Molecular genetic testing is routinely performed to identify hereditary cases. In addition, understanding the molecular basis of both hereditary and sporadic MTC has led to the development of targeted therapy with tyrosine kinase inhibitors. Although additional data are needed, tumor mutation status may affect response to targeted therapy. Therefore, it is possible that genetic testing of tumor tissue to predict treatment response, as is currently done for other cancer types, may come into practice in the future.
KW - Familial medullary thyroid carcinoma
KW - Medullary thyroid carcinoma
KW - Multiple endocrine neoplasia
KW - RAS
KW - RET
KW - Tyrosine kinase
UR - http://www.scopus.com/inward/record.url?scp=84937965800&partnerID=8YFLogxK
U2 - 10.1309/AJCPHWACTTUYJ7DD
DO - 10.1309/AJCPHWACTTUYJ7DD
M3 - Review article
C2 - 25972318
AN - SCOPUS:84937965800
VL - 143
SP - 768
EP - 777
JO - American Journal of Clinical Pathology
JF - American Journal of Clinical Pathology
SN - 0002-9173
IS - 6
ER -