RET rearrangements in archival oxyphilic thyroid tumors: new insights in tumorigenesis and classification of Hürthle cell carcinomas?
BACKGROUND
Oncocytic carcinomas (Hürthle cell carcinomas [HCCs]) are commonly considered a subgroup of follicular thyroid carcinomas (FTCs). Recent characterization of a subgroup of "Hürthle cell" papillary thyroid carcinomas (PTCs) was based on the identification of PTC-specific 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.


CONCLUSIONS
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.
Musholt
Petra B
PB
Department of Visceral & Transplantation Surgery, Hannover University Medical School, Clinical Chemistry, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
Imkamp
Florian
F
von Wasielewski
Reinhard
R
Schmid
Kurt W
KW
Musholt
Thomas J
TJ
D018249:Adenoma, Oxyphilic / Q000145:classification / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D008297:Male; D008875:Middle Aged; D015513:Oncogene Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011505:Protein-Tyrosine Kinases; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology
D015513:Oncogene Proteins; D015514:Oncogene Proteins, Fusion; D011505:Protein-Tyrosine Kinases; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; D020794:Receptor Protein-Tyrosine Kinases; C093573:ret-PTC fusion oncoproteins, human