Application of an immunodiagnostic method for improving preoperative diagnosis of nodular thyroid lesions

Background Thyroid cancer is the most common endocrine malignant disease, b ut preoperative diagnosis remains a challenge. Fine-needle aspiration cytol ogy has greatly improved the clinical management of thyroid nodules, but th e preoperative characterisation of follicular lesions is very difficult. Ma ny patients are thus referred to surgery more for diagnosis than for therap eutic necessity. We undertook an international multicentre study to assess the usefulness of immunohistocytochemical staining for two potential marker s of malignant thyrocytes. Methods Expression of galectin-3 and CD44v6 was tested on 1009 thyroid lesi ons (tissue specimens and cytological cell-blocks) and 226 fresh cytologica l samples obtained preoperatively by ultrasound-guided fine-needle aspirati on of thyroid nodules (prospective analysis). The test used monoclonal anti bodies specific for CD44v6 and galectin-3, the indirect avidin-biotin compl ex immunoperoxidase method, and 3-amino-9-ethylcarbazole as substrate. Findings The sensitivity, specificity, positive predictive value, and diagn ostic accuracy of this test method (for coexpression of the two markers) in the prospective analysis were 88%, 98%, 91%, and 97%, respectively. The se nsitivity and specificity of galectin-3 immunodetection alone in discrimina ting benign from malignant thyroid lesions were more than 99% and 98% respe ctively, and the positive predictive value and diagnostic accuracy were 92% and 99%. Interpretation The integration of galectin-3 immunostaining with convention al cytomorphological and clinical diagnostic procedures represents a sensit ive and reliable diagnostic approach for preoperative identification of thy roid carcinomas. This test method improves the diagnostic accuracy of conve ntional cytology and provides the molecular basis for a new nosological ass ignation of the not yet classified thyroid neoplasms of indeterminate malig nant behaviour.