Cancer-specific mRNAs in thyroid carcinomas: detection, use, and their implication in thyroid carcinogenesis

Molecular-based diagnosis ofthyroid carcinomas can be more easily establishedby utilizing specific mRNAs that are expressed in a restricted manner in cancer tissues. Accordingly, several cancer-specific mRNAs in thyroid carcinomas have been identified by means of sequence specific-differential display (SS-DD), serial analysis of gene expression (SAGE) and other new techniques. By using these cancer-specific mRNAs, some new methods of preoperative diagnosis of thyroid carcinomas have been developed. In one such method, Aspiration Biopsy-Reverse Transcription-Polymerase Chain Reaction (ABRP), RNA is extracted from leftover cells within the needle used for fine needle aspiration biopsies (FNABs), thereby allowing cytological and molecular-based diagnoses to be performed simultaneously. ABRP provides both RNA information and a cytological diagnosis without further invasion to the patient. By ABRP detection of cancer-specific mRNAs, papillary, anaplastic and medullary carcinomas and a part of malignant lymphomas can be accurately diagnosed preoperatively. It remains to be clarified why cancer-specific mRNAs, especially those that are overexpressed in fetal tissues, can clearly distinguish benign tissues from carcinomas, while genomic alternations, such as mutations in the RAS or P53 gene cannot. Further, the widely accepted hypothesis of multi-step carcinogenesis cannot explain some of the clinical and experimental findings of thyroid carcinomas. Considering these facts, we propose a novel hypothesis of thyroid carcinogenesis, the "germ-cell carcinogenesis" hypothesis, in which cancer cells derive from the remnants of fetal thyroid germ cells (thyroblasts) instead of normal thyroid follicular cells.