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 clone from a genetically altered cell and thus provides objective information on the origin of the thyroid nodules. Clonality was studied in thyroid nodules using the polymerase chain reaction (PCR) assay in the X-linked human androgen receptor (HUMARA) gene by random X chromosome inactivation in women.

METHODS

DNA samples were obtained from 28 nodules in 21 women. All nodules and non-tumour thyroid tissues were fractioned selectively under a cryostat. Genomic DNA was isolated and digested with HhaI. PCR amplification of the HUMARA locus was performed using PCR mixtures containing [alpha-32P]2'-deoxycytidine 5'-triphosphate. The PCR products were analysed by denaturing gel electrophoresis.

RESULTS

The HUMARA alleles were heterogeneous 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 monoclonal. The monoclonal follicular nodules were larger in size (3.5 versus 2.0 cm, P< 0.05) and had a tendency towards more cystic changes than polyclonal nodules.

CONCLUSION

PCR-based clonality study of thyroid nodules may help to distinguish hyperplastic from neoplastic nodules.