Shattuck TM et al. (2005) Independent clonal origins of distinct tumor foci in multifocal papillary thyroid carcinoma. N Engl J Med 352: 2406–2412

Multifocal papillary thyroid tumors are associated with an increased risk of persistent local disease and regional recurrence after treatment, as well as with lymph-node and distant metastases. A recent study by Shattuck et al. investigated the origins of such multiple distinct thyroid tumor foci, using X-chromosome inactivation.

The researchers assessed DNA from tumor samples taken from 10 women who had undergone thyroidectomy to treat papillary thyroid carcinoma and who had multiple distinct tumor foci. All women were heterozygous for a polymorphism in the HUMARA (X-linked human androgen receptor) gene, and a polymerase chain reaction assay based on this gene was used to compare the patterns of monoclonal X-chromosome inactivation in tumor foci samples.

On comparison of the configurations of X-chromosome inactivation for each patient's individual tumor foci, 5 of the 10 patients showed discordant patterns between discrete foci, indicating that the tumors had independent origins. The remaining five patients showed identical monoclonal configurations in each of either two or three tumor foci, suggesting that the individual foci could have either a shared or a separate clonal origin.

In conclusion, the authors note that when surgery is used to treat multifocal papillary thyroid cancer, any thyroid tissue remaining post-surgery might either contain or be likely to develop further cancer foci that could become recurrences. Their results imply a strong predisposition to the development of new thyroid cancers in such patients, and therefore provide a biological rationale that supports bilateral thyroidectomy and radioablation of the remaining tissue.