PREOPERATIVE DIAGNOSIS OF THYROID PAPILLARY CARCINOMA BY REVERSE-TRANSCRIPTASE POLYMERASE CHAIN-REACTION OF THE MUC1 GENE

As thyroid nodules are common, it is imperative to recommend operation only to those with a high risk of malignancy. Fine-needle aspiration (FNA) biopsy, which is widely used for this purpose, is limited by the considerable rate of nondiagnostic or non-interpretable conclusions. Therefore, it is highly desirable to acquire a new diagnostic means fo r thyroid cancer. We have recently described a marked over-expression of the MUCI gene in thyroid papillary-carcinoma tissue, as compared wi th various benign thyroid pathologies. As the amount of mRNA obtainabl e by FNA is not amenable to hybridization analysis, we amplified the m RNA sequence of the MUCI-gene upstream of the variable number tandem r epeat array using the reverse-transcription polymerase chain reaction (RT-PCR). Seven out of 8 FNA samples obtained from thyroid papillary c arcinoma resulted in 336 and 309 base-pair products. In contrast, in a ll 13 FNA samples obtained from various benign pathologies, only the s maller RT-PCR product was observed. Sequence analysis of the RT-PCR pr oducts indicates that alternative splicing of the exon 2 acceptor site accounts for the difference between the 2 amplification products, It is suggested that RT-PCR of the MUCI-gene transcript may add a biomole cular diagnostic dimension to the routine cytological preoperative FNA diagnosis. (C) 1996 Wiley-Liss, Inc.