Prevalence of RET/PTC rearrangement in benign and malignant thyroid nodules and its clinical application
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Fine-needle aspiration cytology (FNAC) is the primary means to distinguish benign thyroid nodules from malignant ones. About 20% of FNAC yields indeterminate results leading to unnecessary or delayed surgery. Many studies of tissue samples, the majority of which are retrospective advocate testing for <I>RET</I> rearrangements as a diagnostic adjunctive tool in thyroid nodules with indeterminate cytological findings. Because of the uncertain prevalence of <I>RET</I> rearrangements, its utility as a tumor marker is still controversial. The goal of this study was to establish the prevalence and the utility of testing for <I>RET</I> rearrangements in FNAC suspicious of cancer in a clinical setting. In this prospective study, we analysed a large series of thyroid aspirates by RT-PCR only and Southern blot on RT-PCR products for type 1 and 3 <I>RET</I> rearrangements. Results were compared with clinical findings, cytological diagnosis and final histopathology. By the higher sensitive Southern-blot on RT-PCR method, RET rearrangements were present in 36% of papillary thyroid carcinomas (<I>RET/PTC-1</I>, 12%; <I>RET/PTC-3</I>, 20%; both, 4%) and of 13.3% of benign nodules. By means of RT-PCR only, <I>RET</I> rearrangements were disclosed only in 14.3% of PTC and in 3.6% of benign nodules. No significant correlation was found between <I>RET</I> rearrangements and clinicopathological features of patients. These results indicate that molecular testing of thyroid nodules for <I>RET/PTC</I> must take into account of its high prevalence in benign nodules, inducing false positive diagnoses when the highly sensitive assay Southern-blot on RT-PCR is used. Its searching by means of RT-PCR only, has a specificity superior of conventional cytology and can be used to refine inconclusive FNAC.
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