Cells producing cathepsins D, B, and L in human breast carcinoma and their association with prognosis
| Autor: | Endre Kalman, Denise Najjar, Robert G. Somers, Ierachmiel Daskal, Ella Gorodetsky, Tamara T. Lah, Patrick Brennan |
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| Rok vydání: | 2000 |
| Předmět: |
Adult
Pathology medicine.medical_specialty Stromal cell Cathepsin L Cathepsin D Breast Neoplasms E-64 Cathepsin B Pathology and Forensic Medicine chemistry.chemical_compound Cytosol Endopeptidases Biomarkers Tumor medicine Humans Aged Aged 80 and over Cathepsin biology Macrophages Carcinoma Ductal Breast Myoepithelial cell Epithelial Cells Middle Aged Prognosis Cathepsins Immunohistochemistry Cysteine Endopeptidases chemistry Tumor progression biology.protein Female Neoplasm Recurrence Local Stromal Cells Carcinoma in Situ |
| Zdroj: | Human Pathology. 31:149-160 |
| ISSN: | 0046-8177 |
| DOI: | 10.1016/s0046-8177(00)80214-2 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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