RET rearrangements in archival oxyphilic thyroid tumors: New insights in tumorigenesis and classification of Hürthle cell carcinomas?

Petra B. Musholt, Florian Imkamp, Reinhard Von Wasielewski, Kurt W. Schmid, Thomas J. Musholt, Alan P.B. Dackiw, Martha A. Zeiger, Allan Siperstein

Research output: Contribution to journalArticlepeer-review

Abstract

Background. Oncocytic carcinomas (Hürthle cell carcinomas [HCCs]) are commonly considered a subgroup offollicular thyroid carcinomas (FTCs). Recent characterization of a subgroup of "Hürthle cell" papillary thyroid carcinomas (PTCs) was based on the identification of PTC-speciflc RET hybrid oncogenes in HCCs. Methods. We examined 27 HCCs, 4 oxyphilic FTCs, 5 oxyphilic PTCs, 2 poorly differentiated carcinomas arising from HCCs (HCC-UTCs), and 16 oxyphilic adenomas. Total RNA was extracted from paraffin-embedded thyroid neoplasms by a novel macrodissection technique that uses a cylindric punch. After reverse transcription-polymerase chain reaction-based screening for RET rearrangements, the samples were tested for all known RET/PTC 1 to 11 hybrids with the use of artificially constructed chimeric sequences as controls. Results. The elimination of C cells by punching dissection significantly reduced RET wild-type expression. RET hybrid oncogenes (7x RET/PTC1, 1x RET/PTC1L, 2x RET/PTC3, 5 uncharacterized RET/PTCx) were demonstrated in 7 of 27 HCCs, in 0 of 4 oxyphilic FTCs, in 4 of 5 oxyphilic PTCs, in 1 of 2 HCC-UTCs, and in 3 of 16 oxyphilic adenomas. Conclusion. Our results suggest that the expression of rearranged RET hybrid oncogenes (1) is present in a similar percentage of HCCs when compared with the literature on nonoxyphilic PTCs, (2) defines PTC-like HCCs better than histomorphologic characterization, (3) excludes HCCs as a subgroup of FTCs, and (4) may play a role in the early tumorigenesis of oncocytic tumors.

Original languageEnglish (US)
Pages (from-to)881-889
Number of pages9
JournalSurgery
Volume134
Issue number6
DOIs
StatePublished - Dec 2003

ASJC Scopus subject areas

  • Surgery

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