title: Molecular profile and clinical-pathologic features of the follicular variant of papillary thyroid carcinoma. An unusually high prevalence of ras mutations.
abstract: The follicular variant (FV) of papillary thyroid carcinoma is characterized by a follicular growth pattern and cytologic features of papillary carcinoma. ret/PTC rearrangements are common in classic papillary thyroid carcinoma (PTC) and PAX8-PPAR gamma and ras mutations in follicular thyroid carcinoma. Their prevalence in FV has not been established. We studied these genetic alterations and clinical-pathologic features in 30 FV cases and compared those with 46 non-FV papillary carcinomas. FV cases revealed 1 ret/PTC rearrangement (3%) and 13 ras mutations (43%). Non-FV cases harbored 13 ret/PTC (28%) (P = .006) and no ras mutations (P = .0002). No PAX8-PPAR gamma was found in either group. FV cases demonstrated a significantly higher prevalence of tumor encapsulation, angiovascular invasion, and poorly differentiated areas and a lower rate of lymph node metastases. These data indicate that the FV of papillary carcinoma has a distinct set of molecular alterations and is characterized by a high frequency of ras point mutations.
authors.affiliation: Departments of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, 231 Albert Sabin Way, PO Box 670529, Cincinnati, OH 45267-0529, USA.
authors.forename: Zhaowen
authors.initials: Z
authors.lastname: Zhu
authors.forename: Manoj
authors.initials: M
authors.lastname: Gandhi
authors.forename: Marina N
authors.initials: MN
authors.lastname: Nikiforova
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Fischer
authors.forename: Yuri E
authors.initials: YE
authors.lastname: Nikiforov
mesh_terms: D000328:Adult; D002291:Carcinoma, Papillary / Q000235:genetics / Q000473:pathology; D018265:Carcinoma, Papillary, Follicular / Q000235:genetics* / Q000556:secondary*; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D015321:Gene Rearrangement; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008297:Male; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; D017354:Point Mutation; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors; D018160:Receptors, Cytoplasmic and Nuclear; D015534:Trans-Activators; D014157:Transcription Factors