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This animal model clearly supports the concept that in thyroid carcinogenesis, there is a very long latency period between the mutational event and the developement of malignant changes. This contradicts previous studies using a higher stimulation of thyrocyte proliferation by iodine deficiency, where malignancies were detected after much shorter time intervals (Axelrad & Leblond 1955). Large doses of iodine may induce thyroid carcinomas (Correa & Welsh 1960). We showed that mild iodine excess is not necessarily associated with the formation of thyroid malignant neoplasms, but when combined with a mutagen, carcinomas arise with high frequency. These data on mild forms of high iodine intake thus put a note of caution to a long term-use of high iodine. It was shown that euthyreosis is best protection against thyroid cancer before environmental hazards are effective. The well-defined setting in these experiments clearly demonstrates that mutational lesions acquired by radiation are clinically silent over a long period of time. It is tempting to use such a model to search for candidate genes altered by mutagens, but which are not changed in thyroid adenomas found under control conditions. The definition of such changes may then have important implications for the characterization of the malignant potential of a given adenoma well before cytological or histological changes occur.

The use of molecular assays to analyze clinical tissues in the diagnosis and management of thyroid cancer, similar to other tumors, will likely allow for more accurate characterization of the aggressiveness of individual tumors and may allow for the early diagnosis of recurrence. The application of these methods to thyroid nodules and nodal metastases is less encumbered by difficulties arising from amplification of transcripts in non-thyroid cells. For these tissues, these assays are likely to be used clinically in the near-future. New data arising from cDNA arrays identifying novel markers of malignancy or tumor aggressiveness make this a growing area of interest. The use of molecular assays in diagnosing distant metastases is more problematic due to issues with ectopic expression of either full length or splice variants of genes thought to be thyroid-specific. Assay quantitation is a complex problem owing to variability in the level of expression of “housekeeping” genes and the variety of phlebotomy and RT-PCR methods reported. Additional research in this area is clearly required before a recommendation can be given regarding clinically applicability of these tests.