Analysis of ret/PTC gene rearrangements refines the fine needle aspirationdiagnosis of thyroid cancer

Papillary carcinoma (PC) represents the most common malignancy of the thyro id gland. Therefore, the assessment of fine needle aspiration biopsies of t hyroid nodules rests heavily on the identification of nuclear features of P C. The ret/PTC oncogene, formed by several gene rearrangements, is specific for PC among thyroid tumors. In this study we examined thyroid aspirates f or the presence of ret/PTC gene rearrangements by RT-PCR and Southern hybri dization. We prospectively collected thyroid aspirates in Cytolyt solution and prepared slides for cytological examination using the ThinPrep method. All remaining material was then used for nucleic acid extraction with subse quent RT-PCR for the housekeeping gene PGK-1 to ensure ribonucleic acid int egrity, for thyroglobulin to ensure the presence of follicular epithelial c ells, and for the three most common ret/PTC gene rearrangements (ret/PTC-1. -2, and -3). The results of the first 73 cases with surgical follow-up wer e correlated with the cytological diagnosis and final histopathology. ret/P TC gene rearrangements were detected in 17 of 33 samples (52%) that were PC on histopathology; the presence of gene rearrangements was confirmed by mo lecular analysis of corresponding surgically resected frozen tissue. There were no false positives. The identification of ret/PTC gene rearrangements refined the diagnosis of PC in 9 of 15 specimens (60%) that would otherwise have been considered indeterminate and in 2 of 6 that were considered insu fficient for cytological diagnosis. The results indicate that RT-PCR for re t/PTC is a specific marker that can be applied to fine needle aspiration bi opsies and improves the diagnosis of malignancy when used as an adjunct to traditional cytology.