Molecular Features of Follicular Variant Papillary Carcinoma of Thyroid: Comparison of Areas with or without Classical Nuclear Features
Guven Guney, Gaye Guler Tezel, Kemal Kosemehmetoglu, Engin Yilmaz, Reyhan Ersoy, Bekir Cakir, Gulnur Guler. Yildirim Beyazit University Ankara Ataturk Research and Education Hospital, Ankara, Turkey; Hacettepe University, Ankara, Turkey
Background: The purpose of this study was to compare the genetic background of different areas in follicular variant papillary thyroid carcinomas (FVPTC) with or without classical nuclear changes.
Design: Sixteen cases of FVPTC were included to our study. In all 16 cases tumor was well demarcated from surrounding thyroid tissue and they had areas with both full (tumoral areas) and none of the (non-tumoral areas) nuclear changes of papillary carcinoma. DNA is obtained by laser microdissection of both morphological tumoral and non-tumoral areas and point mutations for NRAS codon 61, HRAS codon 61, and BRAF were investigated by direct sequencing. In 11 cases, RT-PCR was performed for the presence of PAX8-PPARγ and RET/PTC1-3 gene rearrangements. Point mutation for NRAS 61 was also studied in 15 colloidal nodules by direct sequencing.
Results: Seven cases (44%) showed at least one mutation; 2 cases (13%) had the same mutation in both tumoral and non-tumoral areas, while in rest only tumoral areas were mutated. None of the studied 11 cases demonstrated RET/PTC1-3 gene rearrangement and in only one case PAX8-PPARγ gene rearrangement was found. Six cases (38%), one of which was both in tumoral and non-tumoral areas, established NRAS codon 61 mutation. Neither HRAS codon 61 nor BRAF were mutated in all cases. Fifteen colloidal nodules were also wild type for NRAS codon 61.
Conclusions: Our findings suggest that NRAS codon 61 point mutations and PAX8-PPARγ gene rearrangement are early events in thyroid carcinogenesis and may be established in selected cases quite before the morphological/phenotypical features fully developed. Therefore, analysis of NRAS codon 61 point mutation seems to be useful especially in diagnosis of follicular variant papillary carcinoma and in cytological specimes with diagnosis of atypia of undetermined significance.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 28, Tuesday Afternoon