engleski

Molecular diagnostics of thyroid cancer

New insights into the molecular-genetic basis of thyroid cancer can be applied in diagnostics to discover new molecular markers and diagnostic procedures. Molecular markers and methods have several different applications in the treatment of patients with thyroid cancer. They can serve for screening, making diagnosis, determining prognosis, and for early detection of residual and recurrent disease in postoperative follow-up of patients. Mutations in the RET gene, which are associated with inherited medullary carcinoma of the thyroid are analyzed for screening. Mutations in the RET gene have been found in more than 90 % of patients with inherited medullary carcinoma of the thyroid, and they are associated with very high risk for development of medullary carcinoma of the thyroid. All first-degree relatives (parents, siblings, and children) of a person known to have inherited medullary carcinoma of the thyroid are tested for mutations in the RET gene. If mutations are found they can be offered a prophylactic thyroidectomy or regular controls. Analysis of molecular markers in fine-needle aspiration samples of thyroid nodules could help in making preoperative diagnosis in cases in which decisive diagnosis regarding malignancy can’ t be made on the basis of cytological analysis. Patients with indeterminate cytological diagnosis regarding malignancy are being surgically treated for diagnostic purposes although most of them have benign thyroid lesions. Introduction of reliable molecular markers which would increase accuracy of preoperative diagnosis could spare some of these patients unnecessary surgery. Numerous markers have been studied: galectin-3, CD44v6, human telomerase reverse transcriptase (hTERT), oncofetal fibronectin, RET/PTC gene rearrangements, mucin-1, high mobility group I(Y) (HMGI(Y)), HBME-1, and others. The expression of these markers has been analyzed by immunocytochemical methods and by reverse transcription - polymerase chain reaction (RT-PCR). Analysis of these markers hasn’ t been included so far in the routine protocols for treatment of patients with thyroid cancer. Nevertheless, some of these markers (eg. galectin-3 detected immunocytochemically) have shown high diagnostic accuracy in identification of malignant thyroid lesions. In an attempt to improve diagnostic accuracy, a combined use of a panel of markers has been analyzed in several studies. Recently published results of transcriptomic analyses (cDNA microarrays) identified new potential markers that could show higher diagnostic accuracy than markers studied so far. It has also been studied whether analysis of the expression of certain markers in thyroid tissue samples after thyroidectomy or fine-needle aspiration samples can help to determine prognosis. Markers studied for that purpose are: p53, p27, cyclin D1, vascular endothelial growth factor (VEGF), mucin-1, pituitary tumor transforming gene (PTTG), mutations in BRAF gene, RET/PTC gene rearrangements, and others. It has been shown, for example, that overexpression of mucin-1 is statistically significantly associated with shorter relapse-free survival in patients with papillary carcinoma of the thyroid. But, none of the markers studied so far has been included in the routine protocols for treatment of patients with thyroid cancer due to a lack of clinically relevant results repeated in different studies on large sample. Measurement of serum thyroglobulin as a marker for recurrent or residual disease is a part of routine postoperative follow-up for patients with differentiated thyroid cancer. But this method has some limitations. Circulating antithyroglobulin antibodies, if present, can interfere with serum thyroglobulin measurement. Also, the measurement of serum thyroglobulin requires previous thyroxine withdrawal or administration of expensive recombinant human thyrotropin (TSH). Detection of circulating thyroid cells by RT-PCR or real-time RT-PCR has been studied as a potential more reliable marker that could replace serum thyroglobulin measurement. In most of these studies thyroglobulin mRNA has been studied as a specific marker for the presence of circulating thyroid cells. Results of different studies regarding the value of this marker are conflicting. The value of this marker is significantly diminished by positive finding of thyroglobulin mRNA in healthy persons reported in several studies. In smaller number of studies other markers in addition to thyroglobulin (thyrotropin receptor, thyroid peroxidase (TPO), and sodium/iodide symporter (NIS)) have been studied. Detection of circulating tumor cells as a marker for local relapse or presence of distant metastases in patients with medullary carcinoma of the thyroid has been studied in only few studies. As markers in these studies, CK20, calcitonin, and carcinoembryonic antigen (CEA) have been analyzed by RT-PCR.

Thyroid cancer ; RT-PCR

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