MARKED INCREASES IN CATHEPSIN-B AND CATHEPSIN-L ACTIVITIES DISTINGUISH PAPILLARY CARCINOMA OF THE THYROID FROM NORMAL THYROID OR THYROID WITH NONNEOPLASTIC DISEASE

Cathepsin B (CB) and cathepsin L (CL) are cysteine endopeptidases invo lved in the processing of thyroglobulin (Tg) in the normal thyroid. As thyroglobulin expression is frequently altered in thyroid carcinomas, we have analyzed 42 human thyroid tissues from 40 patients to study t he effect of malignant transformation on the expression of these endop eptidases. Our samples included 18 cases of papillary carcinoma (of wh ich 10 also had matched adjacent normal thyroid tissue), 6 cases of no rmal thyroid from autopsy patients, 1 case of follicular carcinoma, 2 cases of medullary carcinoma, 2 cases of follicular adenoma, 3 cases o f Hashimoto's thyroiditis (HT) and 10 samples from 8 patients with mul ti-nodular goiter (MNG). Enzyme-specific activities were increased 15- fold for CB and 9-fold for CL in papillary carcinoma compared with nor mal adjacent thyroid tissue or normal thyroid from autopsies. CB mRNA content was also markedly increased in papillary carcinoma compared wi th normal thyroid, primarily due to elevated levels of the 2.2-kb CB m RNA transcript. In thyroids with nonneoplastic diseases, including MNG and HT, there was no significant increase in either CB or CL enzyme a ctivities nor CB mRNA levels compared with normal thyroids from non-ca ncer cases. Immunohistochemical studies on papillary carcinomas reveal ed increased CB staining in papillary carcinoma cells, with prominent staining close to the basement membranes of many of the neoplastic cel ls. Our observations suggest that CB and CL enzyme activities are pote ntially useful new biochemical markers for distinguishing papillary ca rcinoma of the thyroid from non-neoplastic thyroid from non-neoplastic thyroid disease. (C) 1996 Wiley-Liss, Inc.