The New Technologies section will provide periodic updates on how advances in molecular and cellular biology are being utilized to develop new diagnostic and therapeutic approaches to thyroid disease. It must be emphasized that the majority of studies reported in this section are new, highly experimental, and not ready for implementation into daily medical practice.

What is the status of Gene Therapy approaches for treatment of thyroid cancer? Will Gene Therapy find an application in the treatment of thyroid disease? Several approaches are currently being considered that involve introduction of specific genes into thyroid cancer cells using gene therapy. This approach may involve introducing "suicide genes" into thyroid cancer cells with the purpose of killing the tumor cells specifically. The use of gene promoter sequences specific for thyroid cells appears promising for expression of toxic genes in thyroid cancer cells in preclinical animal studies. For example, see Adenoviral-mediated gene therapy for thyroid carcinoma using thymidine kinase controlled by thyroglobulin promoter demonstrates high specificity and low toxicity. Thyroid. 2001 Feb;11(2):115-23.

Alternatively, scientists are examining the feasibility of introducing the gene responsible for iodine transport, the sodium/iodide symporter, into thyroid cancer cells that have lost the ability to take up radioactive iodine. A major limitation for treatment of some thyroid cancers is the progressive reduction in the ability of these cancers to take up radioactive iodine. Scientists are working on strategies to enhance the expression of the gene that controls iodine uptake, known as the sodium iodide symporter. To review these types of studies, see Adenovirus-mediated transfer of the thyroid sodium/iodide symporter gene into tumors for a targeted radiotherapy Cancer Res 2000 Jul 1;60(13):3484-92 and Adenovirus-mediated tumor suppressor p53 gene therapy for anaplastic thyroid carcinoma in vitro and in vivo. J Clin Endocrinol Metab. 2000 Nov;85(11):4081-6. For an overview of experimental studies and future directions, see The sodium iodide symporter and its potential role in cancer therapy. J Clin Endocrinol Metab. 2001 Jul;86(7):3327-35 and Clinical review 131: gene therapy for thyroid cancer: where do we stand? J Clin Endocrinol Metab. 2001 Jul;86(7):2923-8.

Can the PCR (polymerase chain reaction) technique be used to enhance the diagnostic accuracy of thyroid cancer diagnosis?

PCR is a highly sensitive rapid technology based on the rapid logarithmic amplification of nucleic acid sequences using short synthetic nucleic acid primers and the enzyme 'Taq Polymerase'. PCR can be used to amplify sequences of our DNA toicheck for mutations in specific genes. Alternatively, the technique of RT-PCR (Reverse Transcription PCR) can be used to amplify copies of RNA transcripts in cellular material, providing a window into which genes are being specifically expressed in certain cell types. This type of approach has been used to determine whether thyroid cancers turn on genes not normally expressed in normal thyroid cells. For example, the expression of oncofetal fibronectin mRNA was much more prevalent in needle biopsy aspirates from specimens ultimately shown to harbor thyroid cancer. See Accurate and objective preoperative diagnosis of thyroid papillary carcinomas by reverse transcription-PCR detection of oncofetal fibronectin messenger RNA in fine-needle aspiration biopsies Cancer Res 1998 Nov 1;58(21):4913-7 An overview of the utility of PCR in the diagnosis of genetic abnormalities found in thyroid aspirates may be found in Genetic Analysis in Fine-needle Aspiration of the Thyroid: A New Tool for the Clinic. Trends Endocrinol Metab 1999 Sep;10(7):280-285.

Using this sensitive approach for analysis of gene expression, it may be possible to detect the presence of tumor cells that circulate in the patients bloodstream. For example, the RNA transcript for thyroglobulin can be detected by RT-PCR in some patients with thyroid cancer, presumably as a result of the presence of circulating tumor cells in these patients. See Detection of recurrent thyroid cancer by sensitive nested reverse transcription-polymerase chain reaction of thyroglobulin and sodium/iodide symporter messenger ribonucleic acid transcripts in peripheral blood. J Clin Endocrinol Metab. 2000 Oct;85(10):3623-7.  RT-PCR also detected the expression of a gene known as cytokeratin 20 in the blood of some patients with thyroid cancers. It is important to extend these types of studies to larger populations to gain confidence that the sensitivity and specificity of the test will remain high. Expression of cytokeratin 20 in thyroid carcinomas and peripheral blood detected by reverse transcription polymerase chain reaction Br J Cancer 2000 Jan;82(1):157-60.

Will Gene Therapy find an application in the treatment of thyroid disease? Several approaches are currently being considered that involve introduction of specific genes into thyroid cancer cells using gene therapy. This approach may involve introducing "suicide genes" into thyroid cancer cells with the purpose of killing the tumor cells specifically. Alternatively, scientists are examining the feasibility of introducing the gene responsible for iodine transport, the sodium/iodide symporter, into thyroid cancer cells that have lost the ability to take up radioactive iodine. To review these types of studies, see Adenovirus-mediated transfer of the thyroid sodium/iodide symporter gene into tumors for a targeted radiotherapy Cancer Res 2000 Jul 1;60(13):3484-92 and Adenovirus-mediated tumor suppressor p53 gene therapy for anaplastic thyroid carcinoma in vitro and in vivo. J Clin Endocrinol Metab. 2000 Nov;85(11):4081-6

Will endoscopic removal of thyroid nodules soon be the procedure of choice for patients requiring surgery?

An increasing number of reports in small groups of patients indicate a growing experience with this technique. Nevertheless, the numbers of patients operated on remain small, and it is somewhat early to make a definitive recommendation about the relative merits and potential disadvantages of this type of operation. See Endoscopic thyroidectomy for solitary thyroid nodules. Thyroid. 2001 Feb;11(2):161-3.