Oncogenes and growth factors in thyroid carcinogenesis

Normal and neoplastic thyroid tissues express a variety of oncogenes, growth factors, and growth factor receptors. The increased expression of a mutated form or forms of c-myc and c-ras appears to be associated with some epithelial and medullary thyroid carcinomas. In some cases the presence of these oncogenes correlates with less favorable histologic appearance. The possibility of cooperation between oncogene products (myc and ras) in neoplastic development is raised by studies on transformed thyroid cells in culture. Moreover, a tissue-specific oncogene associated with papillary carcinoma recently has been described. The role of excessive growth factor or growth factor receptor expression in thyroid carcinoma also has been discussed and may, as with other tumor types, be linked to specific oncogene products (e.g., c-erb-B encoding for the EGF receptor). However, the regulation of oncogenes in various stages of differentiation of thyroid tissues is not well understood. In addition to describing these associations with thyroid carcinoma and putative unchecked growth factor action in the development of neoplasia, more direct demonstrations of a causal relationship are necessary. Thus, one needs to overexpress oncogenes/growth factors in normal cell lines (as has been described in this review) and observe whether cellular transformation or dedifferentiation or both occur. The ability to specifically block oncogene or growth factor expression in neoplastic cell lines at the RNA or protein level (with antisense oligonucleotides or monoclonal antibodies, respectively) should provide important information about the pathogenetic importance of these factors. It may be anticipated that reversing the overexpression of certain oncogenes can lead to normal cellular proliferation, morphology, and differentiation. The knowledge obtained from investigating the associations of oncogenes and growth factors with thyroid cancer should provide insight into the mechanisms involved in cell growth and differentiation and in the biochemical steps involved in neoplastic transformation. New insights into these processes may lead to specific therapeutic measures designed to block aberrant expression of the cellular products involved in neoplasia. A more complete understanding of the role of oncogenes in thyroid cancer also may lead to the development of specific tumor markers that may be useful in the early diagnosis of thyroid cancer and the follow-up of therapeutic maneuvers. If specific markers can be identified, analysis of fine-needle aspiration specimens of the thyroid or imaging techniques (using for example, oncogene-specific monoclonal antibodies) could be added to the diagnostic armamentarium for thyroid disease.