Molecular basis off hurthle cell papillary thyroid carcinoma.
Among thyroid neoplasms, Hurthle cell tumors (HCTs) have traditionally been a distinct diagnostic category. Hurthle cell adenomas are encapsulated follicular lesions with benign behavior. Hurthle cell carcinomas exhibit unequivocal capsular and/or vascular invasion; they are aggressive tumors with a poor prognosis. Recently, Hurthle cell papillary thyroid carcinomas (PTCs) have been identified on morphological grounds. We hypothesize that a subset of HCTs represent PTC with clinical, histological, and immunohistochemical features based on specific molecular events. ret/PTC gene rearrangements give rise to novel oncogenes that are unique to PTC. We studied a group (n = 50) of HCTs for ret/PTC gene rearrangements. Tumors were examined for papillary differentiation by light microscopic evaluation of nuclear features, by RT-PCR for ret/PTC gene rearrangements, and by immunohistochemistry for ret. Among 24 noninvasive tumors, 13 contained ribonucleic acid for ret/PTC-1, -2, or -3, and 9 of these were immunoreactive for ret. Among 19 Hurthle cell carcinomas, 15 had focal nuclear hypochromasia with grooves and/or inclusions; expressed transcripts of ret/PTC-1, -2, or-3; and exhibited ret positivity. Tumors with ret/PTC gene rearrangements tended to have lymph node metastases rather than hematogenous spread. Our results indicate that a subset of HCTs exhibit features of PTC that are attributable to specific gene rearrangements, resulting in expression of ret/PTC oncogenes. These data support subclassification of HCTs into three groups: Hurthle cell adenomas, Hurthle cell carcinomas, and Hurthle cell PTC.
Cheung
C C
CC
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, University of Toronto, Ontario, Canada.
Ezzat
S
S
Ramyar
L
L
Freeman
J L
JL
Asa
S L
SL
D000231:Adenocarcinoma, Papillary / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology
D015514:Oncogene Proteins, Fusion