BACKGROUND: Molecular testing of thyroid malignancies, in combination with cytologic and histologic examination, is becoming increasingly attractive as a tool for refining traditional morphologic diagnosis. The molecular changes associated with follicular thyroid carcinoma (FTC) are point mutations in RAS oncogenes or the presence of PAX8/PPARG (paired box 8/peroxisome proliferator-activated receptor gamma) rearrangement. METHODS: We developed and validated a clinical assay for the detection of PAX8/PPARG rearrangements that uses a 4-color reverse-transcription PCR (RT-PCR) assay and high-resolution fragment analysis. RESULTS: The RT-PCR assay is applicable for detecting the various described fusion transcripts of PAX8/PPARG in formalin-fixed, paraffin-embedded thyroid tissue and in fine-needle aspirate biopsy washes from thyroid nodules. The analytical sensitivity of the assay is 1 abnormal cell in a background of 100-10 000 translocation-negative cells. A comparison of the RT-PCR assay with dual-fusion fluorescence in situ hybridization showed an overall concordance of 95%. With this assay, we obtained a prevalence for the PAX8/PPARG rearrangement in FTC of 62% (13 of 21 cases), compared with a 5% prevalence (3 of 55) for other follicular cell-derived neoplasms. CONCLUSIONS: The introduction of this assay into clinical practice could provide useful information for the diagnosis and possibly for the prognosis and treatment of thyroid cancer in the future.
BACKGROUND: Molecular testing of thyroid malignancies, in combination with cytologic and histologic examination, is becoming increasingly attractive as a tool for refining traditional morphologic diagnosis. The molecular changes associated with follicular thyroid carcinoma (FTC) are point mutations in RAS oncogenes or the presence of PAX8/PPARG (paired box 8/peroxisome proliferator-activated receptor gamma) rearrangement. METHODS: We developed and validated a clinical assay for the detection of PAX8/PPARG rearrangements that uses a 4-color reverse-transcription PCR (RT-PCR) assay and high-resolution fragment analysis. RESULTS: The RT-PCR assay is applicable for detecting the various described fusion transcripts of PAX8/PPARG in formalin-fixed, paraffin-embedded thyroid tissue and in fine-needle aspirate biopsy washes from thyroid nodules. The analytical sensitivity of the assay is 1 abnormal cell in a background of 100-10 000 translocation-negative cells. A comparison of the RT-PCR assay with dual-fusion fluorescence in situ hybridization showed an overall concordance of 95%. With this assay, we obtained a prevalence for the PAX8/PPARG rearrangement in FTC of 62% (13 of 21 cases), compared with a 5% prevalence (3 of 55) for other follicular cell-derived neoplasms. CONCLUSIONS: The introduction of this assay into clinical practice could provide useful information for the diagnosis and possibly for the prognosis and treatment of thyroid cancer in the future.
Authors: J Gregory Powell; Xiying Wang; Brandon L Allard; Mustafa Sahin; Xiao-Li Wang; Ian D Hay; Henry J Hiddinga; Seema S Deshpande; Todd G Kroll; Stefan K G Grebe; Norman L Eberhardt; Bryan McIver Journal: Oncogene Date: 2004-04-29 Impact factor: 9.867
Authors: Marina N Nikiforova; Paul W Biddinger; Christy M Caudill; Todd G Kroll; Yuri E Nikiforov Journal: Am J Surg Pathol Date: 2002-08 Impact factor: 6.394
Authors: Marina N Nikiforova; Roy A Lynch; Paul W Biddinger; Erik K Alexander; Gerald W Dorn; Giovanni Tallini; Todd G Kroll; Yuri E Nikiforov Journal: J Clin Endocrinol Metab Date: 2003-05 Impact factor: 5.958
Authors: Yuri E Nikiforov; David L Steward; Toni M Robinson-Smith; Bryan R Haugen; Joshua P Klopper; Zhaowen Zhu; James A Fagin; Mercedes Falciglia; Katherine Weber; Marina N Nikiforova Journal: J Clin Endocrinol Metab Date: 2009-03-24 Impact factor: 5.958
Authors: James E Fisher; Joseph B Lillegard; Travis J McKenzie; Brian R Rodysill; Peter J Wettstein; Scott L Nyberg Journal: Liver Transpl Date: 2013-03 Impact factor: 5.799
Authors: Crescent R Isham; Brian C Netzel; Ayoko R Bossou; Dragana Milosevic; Kendall W Cradic; Stefan K Grebe; Keith C Bible Journal: J Clin Endocrinol Metab Date: 2014-03-14 Impact factor: 5.958
Authors: L Giovanella; A Campenni; G Treglia; F A Verburg; P Trimboli; L Ceriani; M Bongiovanni Journal: Eur J Nucl Med Mol Imaging Date: 2015-12-23 Impact factor: 9.236