Assessment of ret/PTC-1 rearrangements in neoplastic thyroid tissue using TaqMan RT-PCR.
Among oncogenes studied in thyroid cancers, a specific activated form of c-ret has been found in a minority of papillary thyroid carcinomas (PTCs). In these tumours, c-ret is activated when by somatic rearrangements, the intracellular domain of RET is juxtaposed with the amino-terminal portion of a different donor gene such as H4, thereby generating a chimeric transcript (ret/PTC-1). The functional effects of c-ret activation and its prognostic implications are currently unclear. This study was undertaken to assess the frequency of RET/PTC-1 expression, any distinctive features of positive tumours to which it might be related, and its prognostic importance. Archival material from 88 thyroid neoplasms [50 PTCs, eight anaplastic carcinomas (ATCs), 25 follicular thyroid carcinomas (FTCs) and five follicular adenomas (FAs)] were analysed for ret/PTC-1 and H4 expression using 5' nuclease assay (TaqMan RT-PCR). RNA from the TPC-1 cell line was included as a positive control for c-ret activation. No FTC or FA displayed activation of ret/PTC-1, though all expressed H4. c-ret activation was found in 24% of PTCs (12 of 50), in 87.5% of ATCs (7 of 8), and in 33% of the combined PTC/ATC group. The frequency of c-ret activation in the aggressive ATC variants noted here suggests that ret/PTC-1-positive PTCs might also have a similar poor prognosis and a follow-up study on this cohort is in progress. Ninety per cent of ret/PTC-1-positive tumours failed to express H4, a phenomenon that has not been described previously and which may have considerable bearing on tumour morphology. A statistically significant proportion (58%) of ret/PTC-1-positive, H4-negative PTCs was associated with chronic inflammatory cell infiltration of the tumour and/or the surrounding thyroid. This association has not been reported previously.
Sheils
O M
OM
Department of Histopathology, Trinity College Dublin, Ireland.
O'Leary
J J
JJ
Sweeney
E C
EC
D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D015321:Gene Rearrangement; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D011505:Protein-Tyrosine Kinases; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism; D013967:Thyroiditis, Autoimmune / Q000235:genetics / Q000378:metabolism
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D011505:Protein-Tyrosine Kinases; C093573:ret-PTC fusion oncoproteins, human