CLINICAL-SIGNIFICANCE OF CLONALITY IN THYROID-NODULES

Background Many different neoplastic and hyperplastic thyroid diseases present with clinically apparent thyroid nodules. Clonality analysis indicates whether a nodule arises from the polyclonal proliferation of a group of cells or forms a done from a genetically altered cell and thus provides objective information on the origin of the thyroid nodul es. Clonality was studied in thyroid nodules using the polymerase chai n reaction (PCR) assay in the X-linked human androgen receptor (HUMARA ) gene by random X chromosome inactivation in women. Methods DNA sampl es were obtained from 28 nodules in 21 women. All nodules and non-tumo ur thyroid tissues were fractioned selectively under a cryostat. Genom ic DNA was isolated and digested with HhaI. PCR amplification of the H UMARA locus was performed using PCR mixtures containing [alpha-P-32]2' -deoxycytidine 5'-triphosphate. The PCR products were analysed by dena turing gel electrophoresis. Results The HUMARA alleles were heterogeno us in 18 of 21 patients. Among the 23 nodules from 18 patients, all of the eight papillary thyroid carcinomas were monoclonal. Two solitary nodules from follicular adenomas were monoclonal. Of the 13 follicular nodules from nodular goitres, ten were polyclonal and three were mono clonal. The monoclonal follicular nodules were larger in size (3.5 ver sus 2.0 cm, P < 0.05) and had a tendency towards more cystic changes t han polyclonal nodules. Conclusion PCR-based clonality study of thyroi d nodules may help to distinguish hyperplastic from neoplastic nodules .