Cells producing cathepsins D, B, and L in human breast carcinoma and their association with prognosis

被引:64
作者
Lah, TT
Kalman, E
Najjar, D
Gorodetsky, E
Brennan, P
Somers, R
Daskal, I
机构
[1] Natl Inst Biol, Dept Genet Toxicol & Canc Biol, Ljubljana 1000, Slovenia
[2] Univ Pecs, Sch Med, Dept Pathol, Pecs, Hungary
[3] Albert Einstein Med Ctr, Dept Pathol & Lab Med, Philadelphia, PA 19141 USA
[4] Albert Einstein Med Ctr, Dept Surg, Philadelphia, PA 19141 USA
[5] Albert Einstein Med Ctr, Breast Canc Ctr, Philadelphia, PA 19141 USA
关键词
breast cancer; cathepsins; immunohistochemistry; prognostic factors; tumor markers;
D O I
10.1016/S0046-8177(00)80214-2
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Lysosomal proteinases, cathepsins D, B, and L have been associated with malignant tumor progression and with prognosis in various human carcinomas. In the current study, the immunohistochemical localization of cathepsins in tumor cells was correlated with cathepsin protein concentration in breast carcinoma cytosols from 77 patients. Significant correlation was found for cathepsin D (P < .041) and borderline correlation for cathepsin B (P < .055) but not for cathepsin L. We hypothesize that the poor correlation of cysteine cathepsins was attributable to the fact that they were present not only in malignant epithelial cells, but also in infiltrating macrophages and stromal fibroblasts. In addition, tumor-surrounding myoepithelial cells (42% of tumors) and myofibroblasts (26% of tumors) as well as endothelial cells of neovasculature (10% of tumors) all stained specifically for cathepsin B. Two thirds of tumors co-expressed cathepsins B and L in tumor cells, whereas only 17% of tumors co-expressed all 3 cathepsins. Intense immunostaining for cathepsin D of tumor cells was observed in tumors at high TNM stage and tumors having positive lymph nodes. The expression of cathepsin B was independent of established prognostic factors, whereas intense cathepsin L staining in tumor cells was associated with high histological grade. With respect to prognosis of patient survival, only tumor-cell-associated cathepsin D (P = .042) and myoepithelial cell-associated cathepsin B (P = .061) showed borderline significance. Cathepsins B and L immunostaining in tumor cells was not prognostic. In contrast, cytosolic levels of cathepsin B correlated with higher rate of relapse. Taken together, these results show the diversity in the cellular distribution of cathepsins in human breast carcinoma, presumably reflecting specific regulation and function of each of the cathepsins during tumor progression. Copyright (C) 2000 by W.B. Saunders Company.
引用
收藏
页码:149 / 160
页数:12
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