In situ hybridization and immunohistochemistry study of thyroid peroxidaseexpression in thyroid tumors

Malignant thyroid tumors reportedly exhibit an anomaly in thyroid peroxidas e (TPO) resulting in a lower affinity for monoclonal antibody 47 (mAb 47) i n immunohistochemistry studies. The purpose of the present study was to com pare TPO immunostaining in normal, benign, and malignant thyroid tissue wit h expression of mRNA sequences in four exons of the molecule including the epitope of mAb 47. TPO immunostaining was performed using mAb 47 and a poly clonal antibody (pAb). Messenger RNA expression was investigated by in situ hybridization using probes specific for mRNA sequences in exons 2, 12 (epi tope of mAb), 15, and 17. As expected, pAb immunostaining was significantly positive on all benign tumors and 50% of carcinomas. With mAb 47, little o r no immunostaining was observed in 16 of 17 carcinomas while significantly positive immunostaining was found in normal tissue and benign tumors. In s itu hybridization showed a decrease and heterogeneity in the expression of all mRNA sequences in carcinomas as compared to normal tissue and benign tu mors. Unlike the other three probes, the probe specific for exon 12 hybridi zed strongly with benign tumors but poorly with most carcinomas. Poor hybri dization was usually correlated with defective mAb 47 immunostaining. These results confirm that TPO is expressed in thyroid carcinomas but in smaller amounts than in normal tissue and benign tumors. In malignant tumors, qual itative changes in TPO may also impede mAb 47 immunostaining. In situ hybri dization showed a concomitant decrease in the corresponding TPO mRNA sequen ce. These changes could be due to abnormalities in the maturation of TPO mR NA leading to a different splicing variant.