ScienceDaily (Sep. 22, 2012) ? Screening air-dried fine needle aspirations (FNA) for a panel of genetic mutations linked to follicular or papillary thyroid cancer could reduce the need for diagnostic thyroid surgery, according to data presented at the 82nd Annual Meeting of the American Thyroid Association (ATA) in Qu?bec City, Qu?bec, Canada.
"The ability to detect known mutations linked to thyroid cancer through fine needle aspiration samples is an important advance that may greatly reduce the need for surgery," said Douglas Forrest, PhD, of at National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health.
FNA is currently the most sensitive method to select suspicious thyroid nodules for surgery but is often limited by indeterminate samples. Genetic sequencing for rearrangements (PAX8/PPARG, RET/PTC) and point mutations (BRAF, NRAS, HRAS, KRAS) has arisen as non-surgical method for the thyroid cancer diagnoses. However, until now, these aberrations have only been detected in fresh FNA samples.
A team of researchers led by Markus Eszlinger, PhD, of the University of Leipzig in Leipzig, Germany, has now shown that the detection of these mutations is feasible using FNA smears. Researchers extracted RNA and DNA from 310 routine air-dried FNA smears (164 indeterminate, 57 malignant, 89 non-neoplastic) and corresponding formalin-fixed paraffin-embedded tissue (FFPE) samples (156 follicular adenomas, 32 follicular thyroid carcinomas, 9 follicular variant papillary thyroid carcinomas, 44 papillary thyroid carcinomas, and 69 goiters). They identified PAX8/PPARG and RET/PTC1 rearrangements using qPCR and BRAF and NRAS and HRAS point mutations using high resolution melting (HRM)-PCR and pyrosequencing. No KRAS mutations were detected in the FNA samples.
On average, 8% of routine FNA samples did not allow analysis of a point mutation and 3.9% did not allow analysis of a rearrangement. For the 164 indeterminate samples, BRAF mutations were detected in 1 FNA/1 FFPE sample, NRAS mutations in 12 FNA/21 FFPE samples, HRAS mutations in 3 FNA/7 FFPE samples. PAX8/PPARG was detected in 6 FNA/6 FFPE samples, while RET/PTC was not detected in any indeterminate sample.
Molecular FNA screening increased the sensitivity from 67% (cytology alone) to 75% (cytology and molecular FNA screening) in the total set. In the indeterminate set with 19 FTCs the sensitivity of detecting carcinomas and mutation positive adenomas was 48% and specificity was 99%.
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The above story is reprinted from materials provided by American Thyroid Association, via Newswise.
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Source: http://feeds.sciencedaily.com/~r/sciencedaily/health_medicine/genes/~3/BK30-JQ3Zpw/120923141218.htm
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