Evaluation of a two-year routine application of molecular testing of thyroid fine needle aspirations (FNA) using a 7-gene-panel in a primary referral setting in Germany.

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Evaluation of a two-year routine application of molecular testing of thyroid fine needle aspirations (FNA) using a 7-gene-panel in a primary referral setting in Germany.

Thyroid. 2017 Jan 10;:

Authors: Eszlinger M, Böhme K, Ullmann M, Görke F, Siebolts U, Neumann A, Franzius C, Adam S, Molwitz T, Landvogt C, Amro B, Hach A, Feldmann B, Graf D, Wefer A, Niemann R, Bullmann C, Klaushenke G, Santen R, Tönshoff G, Ivancevic V, Kögler A, Bell E, Lorenz B, Kluge G, Hartenstein C, Ruschenburg I, Paschke R

Abstract
BACKGROUND: Major differences with respect to the diagnostic performance of a "ruling in" approach in the pre-surgical diagnosis of indeterminate thyroid fine needle aspirations (FNAs) have been reported. Therefore, the aim of this prospective multicenter study was to investigate the specific diagnostic impact of mutation testing using a 7-gene-panel in a routine primary referral setting analyzing FNAs from endocrinology and nuclear medicine practices in Germany.
METHODS: RNA and DNA was extracted from 564 routine air-dried FNA smears obtained from 64 physicians and cytologically graded by one experienced cytopathologist. PAX8/PPARG and RET/PTC rearrangements were detected by qPCR, while BRAF and RAS mutations were detected by pyrosequencing. Molecular data were compared to histology and follow-up > 1 year, which were available for 322 out of 348 patients undergoing surgery and 33 out of 74 patients having follow-up. Histology results were obtained from the local routine pathologists, who were blinded to the molecular test results.
RESULTS: BRAF and RET/PTC mutations were associated with carcinoma in 98% and 100% of samples. RAS and PAX8/PPARG mutations were associated with carcinoma in 31% and 0% of samples. 36% of the carcinomas were identified by molecular testing in the atypia of undetermined significance / follicular lesion of undetermined significance (AUS/FLUS) and follicular neoplasm / suspicious for a follicular neoplasm (FN/SFN) categories with malignancy rates of 15% and 17%. Due to a low percentage of RAS mutation-positive carcinoma in combination with a rather high percentage of RAS mutation-positive benign nodules, the positive predictive values of 41% and 36% in the AUS/FLUS and FN/SFN categories offer only limited diagnostic potential.
CONCLUSION: In conclusion, our data suggest that the application of the current 7-gene-panel in a routine primary referral setting does not improve the pre-surgical diagnosis of thyroid FNAs. While the diagnostic relevance of RAS mutations in thyroid tumors needs further investigation, more comprehensive mutation panels with more cancer-specific mutations may improve the pre-surgical diagnosis of thyroid FNAs.

PMID: 28071986 [PubMed - as supplied by publisher]

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