Molecular pathogenesis of thyroid nodules and cancer

Tumours derived from the thyroid follicular epithelium represent an informa tive model for understanding the molecular pathogenesis of multistage tumou rigenesis, which is the prevailing theory on cancer development and progres sion nowadays. The early stages of thyroid tumour development appear to be the consequence of the activation or 'de novo' expression of several proto- oncogenes or growth factor receptors, such as ras, ret, NTRK, met, gsp and the thyrotropin (TSH) receptor. Alterations in the expression pattern of th ese genes are associated with the development of differentiated neoplasms, ranging from benign toxic adenomas (gsp and TSH receptor), to follicular (r os) and papillary (ret/PTC, NTRK, met) carcinomas. They may all be consider ed to be early events of thyroid cell transformation and, for some, experim ental evidence derived from gene transfer studies supports this hypothesis. Alterations in tumour suppressor genes (p53, Rb) are associated instead wi th the most aggressive and poorly differentiated forms of thyroid cancer, i ndicating that, in the thyroid tumourigenic process, they represent late ge netic events, Specific environmental factors (iodine deficiency, ionizing r adiations) have been shown to play a crucial role in promoting the developm ent of thyroid cancer, influencing both its genotypic and phenotypic featur es. Interestingly, a high percentage of genetic lesions causing thyroid can cer originate from gene rearrangements and chromosomal translocations (ret/ PTC, NTRK, Pax-8/PPAR gamma) a finding which, being a rare event in most ep ithelial tumours, makes the molecular pathogenesis of thyroid cancer unique . The uninterrupted flow of information on the molecular genetics of thyroi d nodules and cancer will broaden the correlation between genotype and phen otype and will also provide important information for the development of mo re accurate preoperative diagnostic tools and more efficient treatment choi ces for the different forms of thyroid cancer.