RAS point mutations and PAX8-PPARγ rearrangement in thyroid tumors: Evidence for distinct molecular pathways in thyroid follicular carcinoma

Marina N. Nikiforova, Roy A. Lynch, Paul W. Biddinger, Erik K. Alexander, Gerald W. Dorn, Giovanni Tallini, Todd G. Kroll, Yuri E. Nikiforov

Research output: Contribution to journalArticle

519 Scopus citations

Abstract

A series of 88 conventional follicular and Hürthle cell thyroid tumors were analyzed for RAS mutations and PAX8-PPARγ rearrangements using molecular methods and for galectin-3 and HBME-1 expression by immunohistochemistry. A novel LightCycler technology-based method was developed to detect point mutations in codons 12/13 and 61 of the H-RAS, K-RAS, and N-RAS genes. Forty-nine percent of conventional follicular carcinomas had RAS mutations, 36% had PAX8-PPARγ rearrangement, and only one (3%) had both. In follicular adenomas, 48% had RAS mutations, 4% had PAX8-PPARγ rearrangement, and 48% had neither. Follicular carcinomas with PAX8-PPARγ typically showed immunoreactivity for galectin-3 but not for HBME-1, tended to present at a younger patient age and be smaller size, and were almost always overtly invasive. In contrast, follicular carcinomas with RAS mutations most often displayed an HBME-1-positive/galectin-3-negative immunophenotype and were either minimally or overtly invasive. Hürthle cell tumors infrequently had PAX8-PPARγ rearrangement or RAS mutations. These results suggest that conventional follicular thyroid carcinomas develop through at least two distinct and virtually nonoverlapping molecular pathways initiated by either RAS point mutation or PAX8-PPARγ rearrangement.

Original languageEnglish (US)
Pages (from-to)2318-2326
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume88
Issue number5
DOIs
StatePublished - May 1 2003

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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    Nikiforova, M. N., Lynch, R. A., Biddinger, P. W., Alexander, E. K., Dorn, G. W., Tallini, G., Kroll, T. G., & Nikiforov, Y. E. (2003). RAS point mutations and PAX8-PPARγ rearrangement in thyroid tumors: Evidence for distinct molecular pathways in thyroid follicular carcinoma. Journal of Clinical Endocrinology and Metabolism, 88(5), 2318-2326. https://doi.org/10.1210/jc.2002-021907