RET ACTIVATION IN ADULT AND CHILDHOOD PAPILLARY THYROID-CARCINOMA USING A REVERSE TRANSCRIPTASE-N-POLYMERASE CHAIN-REACTION APPROACH ON ARCHIVAL-NESTED MATERIAL

Activation of the RET tyrosine kinase domain occurs in a proportion of thyroid papillary carcinomas. Three chromosomal rearrangements have b een described, of which PTC1 is the commonest. Wide differences (2.5-2 5%) in frequency of PTC1 in different populations have been reported; it is not clear whether these are due to environmental factors, racial differences or technical reasons. We have developed a simple and rapi d reverse transcriptase nested polymerase chain reaction (RT-nPCR) met hod enabling the detection of gene expression from single 5 mu m secti ons of formalin-fixed paraffin wax-embedded archival material. We have applied this approach to detect expression of the RET tyrosine kinase domain, allowing identification of RET activation resulting from any rearrangement, whether characterised or not, or from overexpression. A retrospective study was performed on 22 adult and 21 childhood papill ary carcinomas. Thirteen of 22 (59%) adult and 10 of 21 (48%) childhoo d carcinomas showed evidence of RET activation, demonstrating a major role for the RET oncogene in UK thyroid papillary carcinogenesis. This study also shows a similar frequency of RET activation in both childr en and adults. The use of a technique that allows reliable amplificati on of RNA from archival material, using primers chosen in different ex ons so that amplified products are readily distinguished from genomic DNA, will allow correlation of translocations and chromosomal rearrang ements with a variety of specific tumour types.