Identifying genetic alterations in poorly differentiated thyroid cancer: a rewarding pursuit.

The concept of “poorly differentiated thyroid carcinoma” (PDTC) was initially proposed more than 25 yr ago (1,2). It described a subgroup of thyroid carcinomas that seemed to fall, in terms of clinicopathological behaviors and aggressiveness, between the classically defined differentiated papillary thyroid carcinomas (PTC)/follicular thyroid carcinomas (FTC) and the undifferentiated anaplastic thyroid carcinomas (ATC). Over the next 20 yr of research, numerous studies supported the existence of such a clinicopathological entity of thyroid carcinoma, leading to the official inclusion of PDTC as a separate tumor entity in the World Health Organization (WHO) classification of thyroid tumors several years ago (3).

[1]  M. Schott.  RAS Mutations Are the Predominant Molecular Alteration in Poorly Differentiated Thyroid Carcinomas and Bear Prognostic Impact , 2010 .

[2]  Peng Hou,et al.  Genetic alterations in the phosphoinositide 3-kinase/Akt signaling pathway confer sensitivity of thyroid cancer cells to therapeutic targeting of Akt and mammalian target of rapamycin. , 2009, Cancer research.

[3]  M. Xing,et al.  Genetic-targeted therapy of thyroid cancer: a real promise. , 2009, Thyroid : official journal of the American Thyroid Association.

[4]  M. Xing,et al.  Recent advances in molecular biology of thyroid cancer and their clinical implications. , 2008, Otolaryngologic clinics of North America.

[5]  A. Pinchera,et al.  BRAF(V600E) mutation and outcome of patients with papillary thyroid carcinoma: a 15-year median follow-up study. , 2008, The Journal of clinical endocrinology and metabolism.

[6]  P. Hou,et al.  Highly prevalent genetic alterations in receptor tyrosine kinases and phosphatidylinositol 3-kinase/akt and mitogen-activated protein kinase pathways in anaplastic and follicular thyroid cancers. , 2008, The Journal of clinical endocrinology and metabolism.

[7]  M. Ringel,et al.  Dysregulation of the phosphatidylinositol 3-kinase pathway in thyroid neoplasia. , 2008, Endocrinology and metabolism clinics of North America.

[8]  M. Fresno,et al.  BRAF mutation associated with other genetic events identifies a subset of aggressive papillary thyroid carcinoma , 2008, Clinical endocrinology.

[9]  Z. Jehan,et al.  Clinicopathological analysis of papillary thyroid cancer with PIK3CA alterations in a Middle Eastern population. , 2008, The Journal of clinical endocrinology and metabolism.

[10]  M. Xing,et al.  BRAF mutation in papillary thyroid cancer: pathogenic role, molecular bases, and clinical implications. , 2007, Endocrine reviews.

[11]  M. Papotti,et al.  Poorly Differentiated Thyroid Carcinoma: The Turin Proposal for the Use of Uniform Diagnostic Criteria and an Algorithmic Diagnostic Approach , 2007, The American journal of surgical pathology.

[12]  M. Xing,et al.  Gene methylation in thyroid tumorigenesis. , 2007, Endocrinology.

[13]  A. El‐Naggar,et al.  Genetic Alterations and Their Relationship in the Phosphatidylinositol 3-Kinase/Akt Pathway in Thyroid Cancer , 2007, Clinical Cancer Research.

[14]  M. Xing,et al.  BRAF mutation in thyroid cancer. , 2005, Endocrine-related cancer.

[15]  Y. Nikiforov.  Genetic alterations involved in the transition from well-differentiated to poorly differentiated and anaplastic thyroid carcinomas , 2004, Endocrine pathology.

[16]  R. Camp,et al.  ras mutations are associated with aggressive tumor phenotypes and poor prognosis in thyroid cancer. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  A. Fischer,et al.  Molecular profile and clinical-pathologic features of the follicular variant of papillary thyroid carcinoma. An unusually high prevalence of ras mutations. , 2003, American journal of clinical pathology.

[18]  V. Vasko,et al.  Specific pattern of RAS oncogene mutations in follicular thyroid tumors. , 2003, The Journal of clinical endocrinology and metabolism.

[19]  G. Fontanini,et al.  N-ras mutation in poorly differentiated thyroid carcinomas: correlation with bone metastases and inverse correlation to thyroglobulin expression. , 2000, Thyroid : official journal of the American Thyroid Association.

[20]  M. Pierotti,et al.  Selective activation of ras oncogenes in follicular and undifferentiated thyroid carcinomas. , 1994, European journal of cancer.

[21]  C. D. Olinici,et al.  Poorly differentiated ("insular") thyroid carcinoma of the ovary. , 1988, Morphologie et embryologie.

[22]  J. Rosai,et al.  Poorly differentiated (“insular”) thyroid carcinoma: A reinterpretation of Langhans' “wuchernde Struma” , 1984, The American journal of surgical pathology.

[23]  A. Sakamoto,et al.  Poorly differentiated carcinoma of the thyroid. A clinicopathologic entity for a high‐risk group of papillary and follicular carcinomas , 1983, Cancer.