BACKGROUND: The diagnostic limitations of thyroid fine-needle aspiration (FNA), such as the indeterminate category, can be partially overcome by molecular analyses. However, until now, rearrangements have only been detected in fresh FNA material and the number of follicular thyroid carcinomas (FTCs) was rather low in previous studies. We aimed at investigating the impact of point mutations and rearrangement detection in a set of routine air-dried FNA smears with a higher percentage of FTCs. METHODS: RNA and DNA was extracted from 310 FNAs (164 indeterminate, 57 malignant, 89 benign) and corresponding formalin-fixed paraffin-embedded tissue (156 follicular adenomas [FAs], 32 FTCs, 44 papillary thyroid carcinomas [PTCs], 9 follicular variant PTCs, and 69 goiters). PAX8/PPARG and RET/PTC rearrangements were detected by qPCR, BRAF and RAS mutations by high-resolution melting PCR and by pyrosequencing. RESULTS: Forty-seven mutations were detected in the FNAs: 22 BRAF, 13 NRAS, and 3 HRAS mutations, 8 PAX8/PPARG, and one RET/PTC-rearrangement. While the presence of a BRAF and RET/PTC mutation was associated with cancer in 100% of samples each, the presence of a RAS and PAX8/PPARG mutation was associated with cancer in only 12% and 50% of samples, respectively. In the indeterminate group 4 of 25 carcinomas were identified by molecular FNA screening, which increased the sensitivity from 67% (cytology alone) to 75% (cytology plus molecular screening). CONCLUSION: Molecular screening for point mutations and rearrangements is feasible in air-dried FNAs. Although the impact of detecting point mutations and rearrangements in FNAs has most likely been overestimated in previous studies, molecular FNA analyses improve presurgical diagnostics. The detection of BRAF mutations in FNA may improve the choice of surgery and postsurgical treatment. Further data are necessary to elucidate the true impact of detecting RAS and PAX8/PPARG mutations in FNAs. The inclusion of additional rare somatic mutations and miRNA markers might further improve the impact of molecular FNA diagnostics.
BACKGROUND: The diagnostic limitations of thyroid fine-needle aspiration (FNA), such as the indeterminate category, can be partially overcome by molecular analyses. However, until now, rearrangements have only been detected in fresh FNA material and the number of follicular thyroid carcinomas (FTCs) was rather low in previous studies. We aimed at investigating the impact of point mutations and rearrangement detection in a set of routine air-dried FNA smears with a higher percentage of FTCs. METHODS: RNA and DNA was extracted from 310 FNAs (164 indeterminate, 57 malignant, 89 benign) and corresponding formalin-fixed paraffin-embedded tissue (156 follicular adenomas [FAs], 32 FTCs, 44 papillary thyroid carcinomas [PTCs], 9 follicular variant PTCs, and 69 goiters). PAX8/PPARG and RET/PTC rearrangements were detected by qPCR, BRAF and RAS mutations by high-resolution melting PCR and by pyrosequencing. RESULTS: Forty-seven mutations were detected in the FNAs: 22 BRAF, 13 NRAS, and 3 HRAS mutations, 8 PAX8/PPARG, and one RET/PTC-rearrangement. While the presence of a BRAF and RET/PTC mutation was associated with cancer in 100% of samples each, the presence of a RAS and PAX8/PPARG mutation was associated with cancer in only 12% and 50% of samples, respectively. In the indeterminate group 4 of 25 carcinomas were identified by molecular FNA screening, which increased the sensitivity from 67% (cytology alone) to 75% (cytology plus molecular screening). CONCLUSION: Molecular screening for point mutations and rearrangements is feasible in air-dried FNAs. Although the impact of detecting point mutations and rearrangements in FNAs has most likely been overestimated in previous studies, molecular FNA analyses improve presurgical diagnostics. The detection of BRAF mutations in FNA may improve the choice of surgery and postsurgical treatment. Further data are necessary to elucidate the true impact of detecting RAS and PAX8/PPARG mutations in FNAs. The inclusion of additional rare somatic mutations and miRNA markers might further improve the impact of molecular FNA diagnostics.
Authors: P Dalquen; B Rashed; A Hinsch; R Issa; T Clauditz; A Luebke; J Lüttges; W Saeger; K H Bohuslavizki Journal: Pathologe Date: 2016-09 Impact factor: 1.011
Authors: Bálint Tobiás; Csaba Halászlaki; Bernadett Balla; János P Kósa; Kristóf Árvai; Péter Horváth; István Takács; Zsolt Nagy; Evelin Horváth; János Horányi; Balázs Járay; Eszter Székely; Tamás Székely; Gabriella Győri; Zsuzsanna Putz; Magdolna Dank; Zsuzsanna Valkusz; Béla Vasas; Béla Iványi; Péter Lakatos Journal: Pathol Oncol Res Date: 2015-08-11 Impact factor: 3.201
Authors: Amanda L Treece; Nathan D Montgomery; Nirali M Patel; Chris J Civalier; Leslie G Dodd; Margaret L Gulley; Jessica K Booker; Karen E Weck Journal: Cancer Cytopathol Date: 2016-02-16 Impact factor: 5.284
Authors: Marta Kaczmarek-Ryś; Katarzyna Ziemnicka; Szymon T Hryhorowicz; Katarzyna Górczak; Justyna Hoppe-Gołębiewska; Marzena Skrzypczak-Zielińska; Michalina Tomys; Monika Gołąb; Malgorzata Szkudlarek; Bartłomiej Budny; Idzi Siatkowski; Paweł Gut; Marek Ruchała; Ryszard Słomski; Andrzej Pławski Journal: Hered Cancer Clin Pract Date: 2015-03-01 Impact factor: 2.857