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 non-diagnostic or non-interpretable conclusions. Therefore, it is highly desirable to acquire a new diagnostic means for thyroid cancer. We have recently described a marked over-expression of the MUC1 gene in thyroid papillary-carcinoma tissue, as compared with various benign thyroid pathologies. As the amount of mRNA obtainable by FNA is not amenable to hybridization analysis, we amplified the mRNA sequence of the MUC1-gene upstream of the variable number tandem repeat array using the reverse-transcription polymerase chain reaction (RT-PCR). Seven out of 8 FNA samples obtained from thyroid papillary carcinoma resulted in 336 and 309 base-pair products. In contrast, in all 13 FNA samples obtained from various benign pathologies, only the smaller RT-PCR product was observed. Sequence analysis of the RT-PCR products 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 MUC1-gene transcript may add a biomolecular diagnostic dimension to the routine cytological preoperative FNA diagnosis.