Expression of the RET proto-oncogene in papillary thyroid carcinoma and its correlation with clinical outcome.

Abstract

In papillary thyroid carcinoma (PTC), presence of the oncogenes RET/PTC has been described, but their correlation with prognosis is debated. The aim of this study was to investigate the expression of the RET proto-oncogene (RET) and correlate it with clinical outcome. Sixty-one PTCs were analysed for expression of RET and the oncogenes RET/PTC1-4 by polymerase chain reaction of complementary DNA. Twenty-nine PTCs (48 per cent) expressed the RET tyrosine kinase domain (RET-TK). Twelve expressed wild-type RET (WT-RET). One tumour expressed RET/PTC3, one a variant of RET/PTC3, and one RET/PTC1 and WT-RET simultaneously. The remaining 14 expressed RET-TK only. WT-RET expression was detected more frequently in poorly differentiated PTCs (P < 0.05) and in PTCs from patients with aggressive disease (P < 0.01). WT-RET expression remained an independently significant risk factor for aggressive disease when analysed together with other recognized risk factors using a stepwise multiple logistic regression model. Almost half of the PTCs showed RET-TK expression; in only three was this explained by expression of a RET/PTC rearrangement. Instead, expression of WT-RET was detected in 45 per cent of the RET-TK-positive tumours and this expression was an independently significant risk factor for aggressive PTC. Presented in abstract form to the Millennium Meeting of Endocrine Surgeons held by the American Association of Endocrine Surgeons, British Association of Endocrine Surgeons and Swedish Association of Endocrine Surgeons, London, UK, May 2000