Endocrine Abstracts

Papillary carcinoma (PC) represents the most common malignancy of the thyroid gland. Therefore, the assessment of biopsies of thyroid nodules rests heavily on the identification of malignant from benign features. Unfortunately, up to 60% of biopsies are considered inadequate due to sampling artifact, insufficient material, or marked inter-observer variation. Proposed molecular markers of PC include HBME-1, specific cytokeratins such as CK19, and the tyrosine kinase receptor (ret), the latter reflecting a ret/PTC rearrangement. We applied immunohistochemical stains to determine the diagnostic accuracy of these three markers. Classical PC had the highest positivity with staining for HBME-1 in 70%, CK19 in 80%, and ret in 78%. Only rarely are all three markers negative in PC; this panel therefore provides an objective and reproducible tool for the analysis of difficult thyroid nodules. The ret/PTC oncogene, formed by several gene rearrangements, is even more specific for PC among thyroid tumors. We examined thyroid aspirates for the presence of ret/PTC gene rearrangements by RT-PCR and Southern hybridization. The results of the first 73 cases with surgical follow-up were correlated with the cytological diagnosis and final histopathology. ret/PTC gene rearrangements were detected in 52% of samples that were PC on histopathology; the presence of gene rearrangements was confirmed by molecular 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 60% that would otherwise have been considered indeterminate or insufficient for cytological diagnosis. The results indicate that RT-PCR for ret/PTC is a specific marker that can be applied to fine needle aspiration biopsies and improves the diagnosis of malignancy when used as an adjunct to traditional cytology. Such an approach can also be applied to characterize the true nature of cell or origin in unusual cases of hurthle cell lesions.