title: Prevalence of RET/PTC rearrangement in benign and malignant thyroid nodules and its clinical application.
abstract: 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 RET rearrangements as a diagnostic adjunctive tool in thyroid nodules with indeterminate cytological findings. Because of the uncertain prevalence of RET 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 RET 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 RET 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 (RET/PTC-1, 12%; RET/PTC-3, 20%; both, 4%) and of 13.3% of benign nodules. By means of RT-PCR only, RET rearrangements were disclosed only in 14.3% of PTC and in 3.6% of benign nodules. No significant correlation was found between RET rearrangements and clinicopathological features of patients. These results indicate that molecular testing of thyroid nodules for RET/PTC 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.
authors.affiliation: Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, Università Federico II, Via S. Pansini 5, Naples, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Guerra
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Sapio
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Marotta
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Campanile
authors.forename: Maria Ilaria
authors.initials: MI
authors.lastname: Moretti
authors.forename: Maurilio
authors.initials: M
authors.lastname: Deandrea
authors.forename: Manuela
authors.initials: M
authors.lastname: Motta
authors.forename: Paolo Piero
authors.initials: PP
authors.lastname: Limone
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Fenzi
authors.forename: Guido
authors.initials: G
authors.lastname: Rossi
authors.forename: Mario
authors.initials: M
authors.lastname: Vitale
mesh_terms: D000368:Aged; D044963:Biopsy, Fine-Needle; D002277:Carcinoma; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D005188:False Negative Reactions; D005189:False Positive Reactions; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D008297:Male; D008875:Middle Aged; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics / Q000473:pathology; D016606:Thyroid Nodule / Q000235:genetics* / Q000473:pathology
chemical_list: D051096:Proto-Oncogene Proteins c-ret