[Aspiration biopsy-RT-PCR(ABRP): lesson from its success]

Molecular-based diagnosis of thyroid carcinomas can be more easily established by utilizing specific mRNAs that are expressed only in cancer tissues. In a previous study, we introduced a new method of preoperatively diagnosing thyroid carcinomas. This technique, aspiration biopsy-RT-PCR(ABRP), facilitated simultaneous cytological and molecular-based diagnoses by extracting RNA from cells remaining within the needle used for fine needle aspiration biopsies(FNABs). ABRP provides both RNA information and a cytological diagnosis without further invasion to the patient. We proved that by ABRP detection of oncofetal fibronectin(onfFN) mRNA in FNABs, papillary and anaplastic carcinomas are accurately diagnosed preoperatively. Further, by real-time monitoring RT-PCR measuring onfFN mRNA, a fully automated system was established. It is not clarified, however, why cancer-specific mRNAs, especially those overexpressed in fetal tissues, can clearly distinguish benign tissues from carcinomas, while genomic alternation such as mutations in RAS or P53 gene cannot. Further, a widely accepted hypothesis, multi-step carcinogenesis, does not explain some of the clinical and experimental evidence from thyroid carcinomas. Considering these facts, we propose a new concept of thyroid carcinogenesis called "germ-cell carcinogenesis", in which cancer cells are derived from the remnant of fetal thyroid germ cells(thyroblasts) instead of normal thyroid follicular cells.