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RET/PTC and RET Tyrosine Kinase Expression in Adult Papillary Thyroid Carcinomas¹

Molecular Genetics Unit, Kolling Institute of Medical Research (D.L.L., M.M., B.G.R.), and the Departments of Endocrinology (D.L.L., B.G.R.) and Surgery (A.I.G., L.W.D.), Royal North Shore Hospital and University of Sydney, Sydney, Australia; and the Department of Surgery, Karolinska Hospital (J.Z.), Stockholm, Sweden

Address all correspondence and requests for reprints to: Prof. B. G. Robinson, Kolling Institute of Medical Research, Royal North Shore Hospital, St. Leonards, New South Wales 2065, Australia. E-mail: bgr{at}med.usyd.edu.au

The prevalence of RET/PTC rearrangements in papillary thyroid carcinomas (PTCs) varies widely in different studies, and an association of RET/PTC presence with tumor behavior remains to be clarified. A prospective study of 50 adult PTCs examined, using RT-PCR, the prevalence of the 3 main RET rearrangements and also of RET tyrosine kinase (TK) domain sequence expression. The genetic findings were correlated with the MACIS clinical prognostic score and with individual clinical parameters. Three of the patients had been exposed to radiation in childhood or adolescence. Four of the PTCs contained RET/PTC1, confirmed by sequencing, and none contained RET/PTC2 or RET/PTC3. The prevalence of RET rearrangements overall was 8%, but in the subgroup of 3 radiation-exposed patients it was 66.6%. Interestingly, RET tyrosine kinase domain messenger ribonucleic acid was detectable in 70% of PTCs using RET exon 12/13 primers and was detectable in 24% of PTCs using RET exon 15/17 primers. RT-PCR for calcitonin and RET extracellular domain, however, was negative. There was no association between the presence or absence of RET/PTC in the patient’s tumor and clinical parameters. We conclude that RET/PTC1 is the predominant rearrangement in PTCs from adults with a history of external irradiation in childhood. RET TK messenger ribonucleic acid expression is common in PTCs, using RT-PCR, and cannot be used to infer the presence of specific RET rearrangements or of RET activation.

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