Molecular genotyping of papillary thyroid carcinoma follicular variant according to its histological subtypes (encapsulated vs infiltrative) reveals distinct BRAF and RAS mutation patterns Journal Article
| Authors: | Rivera, M.; Ricarte-Filho, J.; Knauf, J.; Shaha, A.; Tuttle, M.; Fagin, J. A.; Ghossein, R. A. |
| Article Title: | Molecular genotyping of papillary thyroid carcinoma follicular variant according to its histological subtypes (encapsulated vs infiltrative) reveals distinct BRAF and RAS mutation patterns |
| Abstract: | The follicular variant of papillary thyroid carcinoma usually presents as an encapsulated tumor and less commonly as a partially/non-encapsulated infiltrative neoplasm. The encapsulated form rarely metastasizes to lymph node, whereas infiltrative tumor often harbors nodal metastases. The molecular profile of the follicular variant was shown to be close to the follicular adenoma/carcinoma group of tumors with a high RAS and very low BRAF mutation rates. A comprehensive survey of oncogenic mutations in the follicular variant of papillary thyroid carcinoma according to its encapsulated and infiltrative forms has not been performed. Paraffin tissue from 28 patients with encapsulated and 19 with infiltrative follicular variant were subjected to mass spectrometry genotyping encompassing the most significant oncogenes in thyroid carcinomas: 111 mutations in RET, BRAF, NRAS, HRAS, KRAS, PIK3CA, AKT1 and other related genes. There was no difference in age, gender, tumor size and angioinvasion between encapsulated or infiltrative tumors. Infiltrative carcinomas had a much higher frequency of extrathyroid extension, positive margins and nodal metastases than encapsulated tumors (P0.05). The BRAF 1799TA mutation was found in 5 of 19 (26%) of the infiltrative tumor and in none of the encapsulated carcinomas (P0.007). In contrast, RAS mutations were observed in 10 of 28 (36%) of the encapsulated group (5 NRAS-Q61R, 3 HRAS-Q61, 1 HRAS-G13C and 1 KRAS-Q61R) and in only 2 of 19 (10%) of infiltrative tumors (P0.09). One encapsulated carcinoma showed a PAX8/PPARγ rearrangement, whereas two infiltrative tumors harbored RET/PTC fusions. Encapsulated follicular variant of papillary thyroid carcinomas have a molecular profile very close to follicular adenomas/carcinomas (high rate of RAS and absence of BRAF mutations). Infiltrative follicular variant has an opposite molecular profile closer to classical papillary thyroid carcinoma than to follicular adenoma/carcinoma (BRAFRAS mutations). The molecular profile of encapsulated and infiltrative follicular variant parallels their biological behavior (ie, metastatic nodal and invasive patterns). © 2010 USCAP, Inc. All rights reserved. |
| Keywords: | adult; clinical article; human tissue; aged; middle aged; cancer surgery; gene mutation; mutation; cancer radiotherapy; mass spectrometry; metastasis; genetic variability; genotype; histology; cancer genetics; oncogene; gene rearrangement; reverse transcriptase polymerase chain reaction; cancer infiltration; molecular typing; thyroidectomy; ras protein; thyroid neoplasms; genes, ras; peroxisome proliferator activated receptor gamma; lobectomy; thyroid papillary carcinoma; b raf kinase; adenocarcinoma, papillary; pik3ca gene; proto-oncogene proteins b-raf; paraffin; akt1 gene; thyroid follicular carcinoma; transcription factor pax8; hras gene; kras gene; nras gene |
| Journal Title: | Modern Pathology |
| Volume: | 23 |
| Issue: | 9 |
| ISSN: | 0893-3952 |
| Publisher: | Nature Research |
| Date Published: | 2010-09-01 |
| Start Page: | 1191 |
| End Page: | 1200 |
| Language: | English |
| DOI: | 10.1038/modpathol.2010.112 |
| PROVIDER: | scopus |
| PMCID: | PMC4573468 |
| PUBMED: | 20526288 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 3" - "Export Date: 20 April 2011" - "CODEN: MODPE" - "Source: Scopus" |
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