BACKGROUND: Papillary thyroid carcinoma (PTC) in young people usually has an aggressive initial presentation, though a good general prognosis despite recurrences in 10%-20% of patients. A number of genetic alterations that activate the mitogen-activated protein kinase (MAPK) pathway have been found in PTC. Some of these alterations have been identified as prognostic factors of PTC in adults. The objective of the current study was to comprehensively characterize all known oncogenic alterations of the MAPK pathway in young people. METHODS: One hundred three PTCs removed from 9 children, 19 adolescents, and 75 young adults were submitted to molecular analyses. RESULTS: Altogether, 57 alterations were found in 56 PTCs (55%) corresponding to V600E BRAF in 20.3%, RAS mutations in 12.6%, RET/PTC 1 in 11.6%, RET/PTC 3 in 8.7%, and rearrangement of NTRK in 1.9%. The prevalence of all alterations increased with age (22.2% in children; 52.6% in adolescents, 51.4% in adults 20-25 years, and 55.1% in adults 25-35 years). Prevalence increased from 39.2% earlier to 61.3% after 20 years mainly due to BRAF mutations. Classic-type PTC was associated with a larger prevalence of alterations, predominantly BRAF and RET/PTC, whereas the follicular variant was chiefly associated with RAS. RET/PTC (1 and 3) was significantly associated with extrathyroid extension (ET) and lymph node metastasis (es) (LNM). This association was found in the adult group. There were no associations of BRAF or RAS mutations with ET or LNM. A 3-year median follow up was available for 90 patients. RET/PTC 1 and 3 was associated with short-term disease dissemination (cervical lymph node recurrences and distant metastases) in young adults (p=0.001). Persistent illness was more prevalent in patients with (15%) than in patients without (7%) genetic alterations. CONCLUSION: PTCs in young patients display a low prevalence of the already identified oncogenic alterations. The increasing prevalence with age is mainly due to V600E BRAF mutation. There is no relation between tumor aggressiveness and BRAF mutation. There is a relation between the presence of RET/PTC (1 and 3) and the histological and clinical short-term aggressiveness of PTC in the population of young adults. Such a relation is not found in children and adolescents.
BACKGROUND:Papillary thyroid carcinoma (PTC) in young people usually has an aggressive initial presentation, though a good general prognosis despite recurrences in 10%-20% of patients. A number of genetic alterations that activate the mitogen-activated protein kinase (MAPK) pathway have been found in PTC. Some of these alterations have been identified as prognostic factors of PTC in adults. The objective of the current study was to comprehensively characterize all known oncogenic alterations of the MAPK pathway in young people. METHODS: One hundred three PTCs removed from 9 children, 19 adolescents, and 75 young adults were submitted to molecular analyses. RESULTS: Altogether, 57 alterations were found in 56 PTCs (55%) corresponding to V600EBRAF in 20.3%, RAS mutations in 12.6%, RET/PTC 1 in 11.6%, RET/PTC 3 in 8.7%, and rearrangement of NTRK in 1.9%. The prevalence of all alterations increased with age (22.2% in children; 52.6% in adolescents, 51.4% in adults 20-25 years, and 55.1% in adults 25-35 years). Prevalence increased from 39.2% earlier to 61.3% after 20 years mainly due to BRAF mutations. Classic-type PTC was associated with a larger prevalence of alterations, predominantly BRAF and RET/PTC, whereas the follicular variant was chiefly associated with RAS. RET/PTC (1 and 3) was significantly associated with extrathyroid extension (ET) and lymph node metastasis (es) (LNM). This association was found in the adult group. There were no associations of BRAF or RAS mutations with ET or LNM. A 3-year median follow up was available for 90 patients. RET/PTC 1 and 3 was associated with short-term disease dissemination (cervical lymph node recurrences and distant metastases) in young adults (p=0.001). Persistent illness was more prevalent in patients with (15%) than in patients without (7%) genetic alterations. CONCLUSION: PTCs in young patients display a low prevalence of the already identified oncogenic alterations. The increasing prevalence with age is mainly due to V600EBRAF mutation. There is no relation between tumor aggressiveness and BRAF mutation. There is a relation between the presence of RET/PTC (1 and 3) and the histological and clinical short-term aggressiveness of PTC in the population of young adults. Such a relation is not found in children and adolescents.
Authors: Pierre Vanden Borre; Alexa B Schrock; Peter M Anderson; John C Morris; Andreas M Heilmann; Oliver Holmes; Kai Wang; Adrienne Johnson; Steven G Waguespack; Sai-Hong Ignatius Ou; Saad Khan; Kar-Ming Fung; Philip J Stephens; Rachel L Erlich; Vincent A Miller; Jeffrey S Ross; Siraj M Ali Journal: Oncologist Date: 2017-02-16
Authors: Julio C Ricarte-Filho; Sheng Li; Maria E R Garcia-Rendueles; Cristina Montero-Conde; Francesca Voza; Jeffrey A Knauf; Adriana Heguy; Agnes Viale; Tetyana Bogdanova; Geraldine A Thomas; Christopher E Mason; James A Fagin Journal: J Clin Invest Date: 2013-10-25 Impact factor: 14.808
Authors: Maria Eleni Nikita; Wen Jiang; Shih-Min Cheng; Feras M Hantash; Michael J McPhaul; Robert O Newbury; Susan A Phillips; Richard E Reitz; Frederic M Waldman; Ron S Newfield Journal: Thyroid Date: 2016-01-07 Impact factor: 6.568