title: Molecular features of follicular variant papillary carcinoma of thyroid: comparison of areas with or without classical nuclear features.
abstract: We aimed to compare the genetic background of different areas in follicular variant papillary thyroid carcinomas (FVPTC) with or without classical nuclear changes. Sixteen cases of FVPTC were included in our study. All tumors were well demarcated from surrounding thyroid tissue and had both areas with nuclear features (WNF) and areas without nuclear features (WONF) of papillary carcinoma. DNA is obtained by laser microdissection from WNF and WONF areas of each case. Point mutations for NRAS codon 61, HRAS codon 61, and BRAF were investigated by direct sequencing. In 11 cases, reverse transcription PCR was performed for the presence of PAX8-PPARɣ and RET/PTC1-3 gene rearrangements. Point mutation for NRAS codon 61 was also studied in 15 colloidal nodules. Seven cases (44 %) showed at least one mutation; two cases (13 %) revealed the same mutation in both WNF and WONF areas, while in the rest only WNF areas were mutated. None of the studied 11 cases demonstrated RET/PTC1-3 gene rearrangement and in only one case PAX8-PPARɣ gene rearrangement was found. Six cases (38 %) showed NRAS codon 61 mutation, involving only WNF areas in five cases and both WNF and WONF areas in one case. Neither HRAS codon 61 nor BRAF mutations were present. Fifteen colloidal nodules were also wild type for NRAS codon 61. Our findings suggest that NRAS codon 61 point mutations and PAX8-PPARɣ gene rearrangement play a role in the FVPTC pathogenesis and may be established before the morphological/phenotypical features fully develop.
authors.affiliation: Department of Pathology, Hitit University Corum Research and Education Hospital, Çorum, Turkey, 19000, Guvenguney61@hotmail.com.
authors.forename: Guven
authors.initials: G
authors.lastname: Guney
authors.forename: Gaye Guler
authors.initials: GG
authors.lastname: Tezel
authors.forename: Kemal
authors.initials: K
authors.lastname: Kosemehmetoglu
authors.forename: Engin
authors.initials: E
authors.lastname: Yilmaz
authors.forename: Serdar
authors.initials: S
authors.lastname: Balci
authors.forename: Reyhan
authors.initials: R
authors.lastname: Ersoy
authors.forename: Bekir
authors.initials: B
authors.lastname: Cakir
authors.forename: Gulnur
authors.initials: G
authors.lastname: Guler
mesh_terms: D000328:Adult; D000368:Aged; D018265:Carcinoma, Papillary, Follicular / Q000235:genetics / Q000473:pathology*; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics; D015321:Gene Rearrangement; D005838:Genotype; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D000072636:PAX8 Transcription Factor; D047495:PPAR gamma / Q000235:genetics; D051761:Paired Box Transcription Factors / Q000235:genetics; D017354:Point Mutation; D013964:Thyroid Neoplasms / Q000235:genetics / Q000473:pathology*
chemical_list: D008565:Membrane Proteins; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D047495:PPAR gamma; D051761:Paired Box Transcription Factors; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human