Shuja S, Murnane M J
Department of Pathology and Laboratory Medicine, Boston University School of Medicine, MA 02118, USA.
Int J Cancer. 1996 May 16;66(4):420-6. doi: 10.1002/(SICI)1097-0215(19960516)66:4<420::AID-IJC2>3.0.CO;2-Y.
Cathepsin B (CB) and cathepsin L (CL) are cysteine endopeptidases involved 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 the effect of malignant transformation an the expression of these endopeptidases. Our samples included 18 cases of papillary carcinoma (of which 10 also had matched adjacent normal thyroid tissue), 6 cases of normal thyroid from autopsy patients, 1 case of follicular carcinoma, 2 cases of medullary carcinoma, 2 cases of follicular adenoma, 3 cases of Hashimoto's thyroiditis (HT) and 10 samples from 8 patients with multi-nodular goiter (MNG). Enzyme-specific activities were increased 15-fold for CB and 9-fold for CL in papillary carcinoma compared with normal adjacent thyroid tissue or normal thyroid from autopsies. CB mRNA content was also markedly increased in papillary carcinoma compared with normal thyroid, primarily due to elevated levels of the 2.2-kb CB mRNA transcript. In thyroids with nonneoplastic diseases, including MNG and HT, there was no significant increase in either CB or CL enzyme activities nor CB mRNA levels compared with normal thyroids from non-cancer cases. Immunohistochemical studies on papillary carcinomas revealed increased CB staining in papillary carcinoma cells, with prominent staining close to the basement membranes of many of the neoplastic cells. Our observations suggest that CB and CL enzyme activities are potentially useful new biochemical markers for distinguishing papillary carcinoma of the thyroid from non-neoplastic thyroid disease.
组织蛋白酶B（CB）和组织蛋白酶L（CL）是半胱氨酸内肽酶，参与正常甲状腺中甲状腺球蛋白（Tg）的加工过程。由于甲状腺球蛋白的表达在甲状腺癌中经常发生改变，我们分析了40例患者的42份人类甲状腺组织，以研究恶性转化对这些内肽酶表达的影响。我们的样本包括18例乳头状癌（其中10例还伴有匹配的相邻正常甲状腺组织）、6例尸检患者的正常甲状腺、1例滤泡状癌、2例髓样癌、2例滤泡性腺瘤、3例桥本甲状腺炎（HT）以及8例多结节性甲状腺肿（MNG）患者的10份样本。与相邻正常甲状腺组织或尸检正常甲状腺相比，乳头状癌中CB的酶特异性活性增加了15倍，CL增加了9倍。与正常甲状腺相比，乳头状癌中CB mRNA含量也显著增加，主要是由于2.2-kb CB mRNA转录本水平升高。在包括MNG和HT在内的非肿瘤性疾病甲状腺中，与非癌病例的正常甲状腺相比，CB或CL酶活性以及CB mRNA水平均无显著增加。对乳头状癌的免疫组织化学研究显示，乳头状癌细胞中CB染色增加，许多肿瘤细胞靠近基底膜处染色明显。我们的观察结果表明，CB和CL酶活性可能是区分甲状腺乳头状癌与非肿瘤性甲状腺疾病的有用新生化标志物。
