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Over the past 15 years, the application of molecular technologies to the study of these neoplasms has elucidated critical genetic pathways associated with the development of specific thyroid tumor types. In papillary thyroid carcinoma (PTC), genetic events involve RET and TRK (rearrangements) and BRAF and RAS (mutations), although RAS mutations are uncommon except in the follicular variant of PTC. These genetic alterations, which rarely overlap in the same tumor, result in signaling abnormalities in the mitogen\u2010activated protein kinase pathway. In contrast, genetic alterations in follicular carcinomas include PAX8\u2010PPAR\u03b3 translocations and RAS mutations while mutations of CTNNB1 and p53 have been implicated in the development and progression of poorly differentiated and undifferentiated (anaplastic) thyroid carcinomas. Germline mutations of RET are responsible for the development of heritable forms of medullary thyroid carcinoma (MTC) while somatic mutations of this oncogene are found in a significant proportion of sporadic MTCs. The results of these studies not only have provided additional approaches to thyroid tumor classification, but also have stimulated the development of novel approaches to tumor diagnosis and additional parameters for prognostic assessment and potential biologic therapeutic strategies. J. Surg. Oncol. 2006;94:662\u2013669. \u00a9 2006 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jso.20700","type":"journal-article","created":{"date-parts":[[2006,11,28]],"date-time":"2006-11-28T03:19:13Z","timestamp":1164683953000},"page":"662-669","source":"Crossref","is-referenced-by-count":140,"title":["Pathology and genetics of thyroid carcinoma"],"prefix":"10.1002","volume":"94","author":[{"given":"Ronald A.","family":"DeLellis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,11,27]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1385\/EP:15:4:319"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1385\/EP:16:4:311"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-005-0065-5"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1836"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1177\/107327480601300205"},{"key":"e_1_2_1_7_2","first-page":"57","volume-title":"Pathology and Genetics of Tumours of Endocrine Organs","author":"LiVolsi VA","year":"2004"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.295.18.2164"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.pas.0000135519.34847.f6"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19940715)74:2<748::AID-CNCR2820740231>3.0.CO;2-H"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-200112000-00002"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(20000415)88:8<1902::AID-CNCR20>3.0.CO;2-Y"},{"key":"e_1_2_1_13_2","first-page":"816","article-title":"Occult micropapillary carcinoma associated with benign follicular thyroid disease and unrelated thyroid neoplasms","volume":"9","author":"Fink A","year":"1996","journal-title":"Mod Pathol"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(85)90115-1"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/328170a0"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90659-3"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1385\/EP:13:1:03"},{"key":"e_1_2_1_18_2","first-page":"1821","article-title":"Development of thyroid papillary carcinomas secondary to tissue specific expression of the RET\/PTC1 oncogene in transgene mice","volume":"12","author":"Santoro M","year":"1996","journal-title":"Oncogene"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65731-8"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1097\/00125480-200111000-00005"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5489.138"},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.pas.0000176432.73455.1b"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.21073"},{"key":"e_1_2_1_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/1-4020-8107-3_12"},{"key":"e_1_2_1_25_2","first-page":"223","article-title":"RET\/NTRK1 rearrangements in thyroid gland tumors of the papillary carcinoma family: Correlation with clinicopathologic features","volume":"4","author":"Bongarzone I","year":"1998","journal-title":"Clin Cancer Res"},{"key":"e_1_2_1_26_2","first-page":"1093","article-title":"Pattern of radiation induced RET and NTRK rearrangements in 191 post\u2010Chernobyl papillary thyroid carcinomas: Biological, phenotypic and clinical implications","volume":"6","author":"Rabes HM","year":"2000","journal-title":"Clin Cancer Res"},{"key":"e_1_2_1_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature00766"},{"key":"e_1_2_1_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/418934a"},{"key":"e_1_2_1_29_2","first-page":"1454","article-title":"High prevalence of BRAF mutations in thyroid cancer. 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