RET/PTC rearrangement in benign and malignant thyroid diseases: a clinical standpoint

Abstract

Cytological examination of fine needle aspiration biopsy is the primary means for distinguishing benign from malignant nodules. However, as inconclusive cytology is very frequent, the introduction of molecular markers in the preoperative diagnosis of thyroid nodules has been proposed in recent years. In this article, we review the clinical implications of preoperative detection of rearrangements of theRETgene (RET/papillary thyroid carcinoma (PTC)) in thyroid nodules. The prevalence ofRET/PTCin PTC depends on the histological subtypes, geographical factors, radiation exposure, and detection method. Initially,RET/PTCwas considered an exclusive PTC hallmark and later it was also found sporadically in benign thyroid lesions. More recently, the very sensitive detection methods, interphase fluorescencein situhybridization (FISH) and Southern blot on RT-PCR amplicons, demonstrated that the oligoclonal occurrence ofRETrearrangement in benign thyroid lesions is not a rare event and suggested that it could be associated with a faster enlargement in benign nodules. For this reason,RET/PTCcannot be considered as an absolute marker of PTC, and its diagnostic application must be limited to assays able to distinguish between clonal and oligoclonal expression. Detection ofRET/PTCby quantitative assays will be useful for diagnostic purposes in cytology specimens when a precise cutoff will be fixed in a clinical setting. Until that time, less sensitiveRET/PTCdetection methods and FISH analysis remain the most appropriate means to refine inconclusive cytology. Future studies with a long follow-up will further clarify the clinical significance of low level ofRETrearrangements in benign nodules.