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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the cellular content and the extracellular release of cathepsins B and D, and of plasminogen activator, in 2 different tumor cell populations before confluence and after late confluence: the HT-29 colon carcinoma cell line, which contains primarily undifferentiated cells, and a subpopulation derived from this cell line, which contains cells committed to differentiation into mucus-secreting goblet cells after confluence. In both populations, cellular cathepsin-B activity increased after confluence, and latent cathepsin B was found in all culture media. In the parental cell line, cellular cathepsin D activity decreased after confluence; however, cathepsin D was secreted at high levels into the extracellular medium. In contrast, in the subpopulation of cells committed to differentiation, cellular cathepsin D activity increased after confluence, and cathepsin D was not secreted into the extracellular medium, but was immunolocalized in the apical brush border of the differentiated cells. Plasminogen activator of urokinase type was identified by immunocytochemistry. Both subconfluent cell populations, and the post-confluent undifferentiated cell population, produced plasminogen activator activity at similar levels. In contrast, in the differentiated postconfluent cells, the production of plasminogen activator activity was markedly lower. Our data show that the differentiation of HT-29 colon carcinoma cells into mucus-secreting cells impairs the secretion of plasminogen activator and cathepsin D, but does not affect cathepsin B.
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PMID:The state of differentiation of HT-29 colon carcinoma cells alters the secretion of cathepsin D and of plasminogen activator. 791 58

Salivary duct carcinoma is an infrequent highly aggressive salivary gland tumor that is histologically similar to ductal carcinoma of the breast. We studied 13 cases by immunohistochemistry for the presence of estrogen and progesterone receptors, cathepsin D, and c-erbB-2 protein to determine whether the similarity to breast carcinoma extended beyond the light microscope to the molecular level and, if so, whether these markers might have therapeutic or prognostic value. Twelve of 13 cases contained sufficient amounts of tumor tissue for evaluation. Of these 12 cases, one (8%) was positive for estrogen receptors, none was positive for progesterone receptors, five (42%) were positive for cathepsin D, and three (25%) were positive for c-erbB-2 protein. Expression of cathepsin D and c-erbB-2 protein does not appear to have prognostic significance in salivary duct carcinoma. The 8% incidence of immunopositivity for estrogen receptors and absence of progesterone receptors in salivary duct carcinoma is considerably less than that seen in breast cancer. Nevertheless, because the occurrence of systemic metastasis in salivary duct carcinoma is such an ominous development largely unresponsive to chemotherapy, antihormonal therapy, such as used in breast cancer, might be considered on a trial basis for those tumors that are estrogen receptor-positive when conventional therapeutic modalities fail.
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PMID:Salivary duct carcinoma. Part II. Immunohistochemical evaluation of 13 cases for estrogen and progesterone receptors, cathepsin D, and c-erbB-2 protein. 791 29

In the natural history of post-menopausal patients with primary breast cancer, high estrogen receptor levels (ER) have been associated with a poor recurrence-free survival. The purpose of this study was to investigate whether there are any biological intratumoral characteristics to support this puzzling clinical observation. In a population of 542 post-menopausal, primary-breast-cancer patients, 3 normal distributions fitted into the frequency distribution curve of the logarithmically transformed ER-EIA values. The biological profiles of the low ER group, and of the intermediate and high ER groups identified in the ER-positive population were compared. Parameters correlated with ER functional aspect (progesterone receptors and PS2), receptors of epidermal growth factor (EGFR), protease cathepsin D and tumor proliferation (deduced from thymidine kinase activity) were analyzed. As previously reported, the levels of progesterone receptors and PS2 increased significantly from the low to the high ER groups. The highest levels of cathepsin D and thymidine kinase which have been previously related to a poor prognosis in breast cancer were found in the low ER group, but high levels were, surprisingly, also found in the high ER group. This study indicates that the ER-positive post-menopausal population is biologically heterogeneous. The high levels of thymidine kinase found in the high ER group suggest that overexpression of ER may be associated with proliferation enhancement, partly explaining the poor spontaneous prognosis related to this subset.
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PMID:Biological heterogeneity of ER-positive breast cancers in the post-menopausal population. 792 97

Low-grade adenosquamous carcinoma of the breast is a variant of metaplastic mammary carcinoma characterized by a locally invasive growth pattern and a low risk for metastases. In this study none of the carcinomas exhibited greater than 5 percent nuclear immunoreactivity for estrogen or progesterone receptors, and as a result they were classified as negative for these receptors. Reactivity for cathepsin D was found in 39 percent of the tumors, largely limited to areas of epidermoid differentiation. Membrane immunoreactivity for HER-2/neu oncogenes was present in glandular components of 46 percent of the carcinomas. Immunoreactivity for p53 (greater than 10 percent of nuclei) was present in 13 percent of the tumors, also in glandular elements. Six different patterns of coexpression of p53, HER-2/neu and cathepsin D were found, the most frequent being the following: HER-2/neu(+), p53(-), cathepsin D(-) (9 cases, 39%); cathepsin D(+), p53(-), HER-2/neu(-) (5 cases, 22%); and the three markers negative (5 cases, 22 percent). Coexpression of the two oncogenes was found in only one tumor which was also positive for cathepsin D. These results indicate that the expression of various immunohistochemical prognostic markers may be heterogeneous and that there may not be a specific pattern of marker coexpression within a carefully defined histologic subtype of mammary carcinoma. Furthermore, characteristics reported to be associated with an unfavorable prognosis (negative hormone receptors, presence of cathepsin D, and expression of oncogenes such as HER-2/neu) may be found in a substantial proportion of tumors that comprise this clinically and histologically low-grade variant of mammary carcinoma. This disassociation between expected prognosis based on expression of current prognostic markers and observed prognosis occurs in other forms of mammary carcinoma. Medullary carcinoma, when diagnosed on the basis of rigorously defined criteria, has an excellent prognosis despite the fact that these tumors are characterized by absence of estrogen and progesterone receptors and a high proliferative rate. The histological classification of mammary carcinomas is itself an important prognostic variable that may take precedence over selected biochemical markers.
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PMID:The pathology of low-grade adenosquamous carcinoma of the breast. An immunohistochemical study. 793 47

Bcl-2 gene product functions to prevent apoptosis in a variety of in vitro and in vivo experiments. The prognostic significance of Bcl-2 protein expression was investigated by immunocytochemistry from paraffin-embedded tissue in a series of 174 women with breast cancer, treated with radical surgery with or without regional radiotherapy, and who had been followed up for the median of 31 years or until death. A minority (25%) of cancers were entirely negative for Bcl-2 protein. Moderate to strong Bcl-2 protein expression (present in 46%) was strongly associated with several favorable prognostic features, such as a low mitotic count, high histological grade of differentiation, and lack of p53 protein expression (P < 0.0001 for each). It was also significantly associated with lack of tumor necrosis, a low S-phase fraction size, low cathepsin D expression, DNA diploidy, and the lobular histological type, but not with the primary tumor size or the axillary nodal status. Women with cancer with moderate to strong Bcl-2 protein expression had more favorable short-term (69% versus 46% alive at 5 years) but similar long-term (29% versus 33% alive at 30 years) disease-specific survival as those with cancer with weak or lacking expression. Bcl-2 protein expression did not have independent prognostic value in a multivariate survival analysis. We conclude that Bcl-2 protein is frequently expressed in breast cancer, and its expression is associated with favorable clinicopathological features.
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PMID:Bcl-2 protein expression and long-term survival in breast cancer. 797 49

Activity of lysosomal proteinases cathepsin B, L and D was studied in tissues of malignant tumors, cancer and normal lymph nodes and mucosal membrane obtained from 18 patients with gastric cancer. The enzymatic activity was distinctly higher in cancer tissues as compared with controls. Activity of cathepsin D was increased in tissues with diminished rate of the tumor differentiation, with pronounced cancer invasion and metastases to regional lymph nodes--the group of highly negative prognosis. At the same time, activity of cathepsin B was increased in tissues of patients with positive prognosis of gastric cancer; negative correlation of cathepsin B activity was observed in both groups of patients. This correlation may be considered as an additional prognostic factor.
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PMID:[Proteolytic enzyme activity in stomach cancer patients with various prognoses]. 807 38

Cathepsins D, B, and L are acidic lysosomal proteinases involved in intracellular protein turnover. Increased levels of these enzymes have been reported to be indicators of aggressive tumor behavior in human and rodent tumors. In breast cancer increased levels of cathepsin D have been reported to be an independent prognostic factor in women with stage I disease. We used standard immunohistochemical techniques on formalin-fixed, paraffin-embedded tissue to examine the levels of cathepsins D, B, and L in 80 carcinomas of the breast and compared that with other indicators of aggressive tumor behavior, including stage of disease, tumor size, nuclear grade, estrogen receptor status, disease recurrence, and 5-year survival rates. Positive granular cytoplasmic staining was detected for cathepsin D in 90% of the tumors, for cathepsin B in two thirds of the tumors, and for cathepsin L in approximately one half of the tumors. Positive staining also was seen in normal breast epithelium, areas of apocrine metaplasia, stromal fibroblasts, and macrophages. Our results did not show a correlation between the expression of cathepsins D, B, and L and other indicators of aggressive tumor behavior. We conclude that the results obtained using polyclonal anticathepsin antibodies do not support the prognostic usefulness of immunohistochemical analysis of these three proteinases in tumor cells in human breast cancer.
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PMID:Immunohistochemical analysis of cathepsins D, B, and L in human breast cancer. 808 57

High cathepsin D (cath-D) concentration in breast cancer cytosol is associated with increased risk of metastasis. To specify the relative contribution of the different cells types responsible for cath-D level in cytosol, we validated semiquantitative cath-D immunoperoxidase staining on formalin-fixed, paraffin-embedded sections, using the M1G8 monoclonal antibody, one of the two antibodies of the cytosolic assay. Using computer-aided image analysis, cath-D level in cancer cells was estimated by integrating both staining intensity in each cell and proportion of stained cells. We confirmed on 41 primary breast cancers a higher expression of cath-D in cancer cells compared with peritumoral mammary glands. Cancer cell staining was mostly in lysosomes and for some invasive ductal carcinomas in large vesicles corresponding to phagosomes. Lymphocytes and fibroblasts were not or were only weakly stained. Macrophages also were stained for cath-D, generally on the periphery of the tumor area. The cytosolic cath-D level was correlated with cath-D expression in cancer cells (r = .76; P = 1 x 10(-4)) rather than with the number of macrophages in the tumor (r = .29; P = .09), as determined by use of the specific anti-CD68 antibody. There was a significant increase in the tissue cath-D level in tumors containing large vesicles compared with tumors without large vesicles. This approach provides a means to separately estimate the prognostic significance of cath-D expression in cancer cells and macrophages when evaluating risk of metastasis.
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PMID:Cathepsin D immunostaining in paraffin-embedded breast cancer cells and macrophages: correlation with cytosolic assay. 808 57

Cathepsin D expression was immunohistochemically tested in 126 formalin-fixed and paraffin-embedded tissues from primary breast cancers. Specific staining was noted in the cytoplasm of tumor cells in 43% of tumors. In 44% of cases cathepsin D was detected in tumor stroma. A total of 63% of the tissue samples stained positive for cathepsin D (tumor and/or stromal staining). In all cases the cathepsin D level was measured in tumor cytosol by radioimmunoassay. Cytosols were considered positive when cathepsin D concentrations of over 40 pmol/mg cell protein were found. Comparison of immunohistochemical and biochemical detection of cathepsin D revealed a 76% concordance rate. Univariate analysis showed a significant correlation of cathepsin D expression with axillary node involvement; no correlation was found with tumor size, tumor grade, steroid receptor status or age of patients. Our results demonstrate a close agreement between the results of biochemical and of immunohistochemical cathepsin D detection.
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PMID:[Cathepsin D expression in primary breast cancer. Comparison of immunohistochemical and biochemical results]. 812 84

Cathepsin D is overexpressed in most primary breast cancers where its concentration is correlated with increased metastatic potential. To investigate the possible role and mechanism of this lysosomal protease in metastasis, we transfected low-metastatic rat tumor cells with wild-type human cathepsin D, or mutated forms obtained by insertion of a KDEL peptide signal responsible for ER retention, or a control KDAS peptide. The overexpressed pro-cathepsin D in wild-type and KDAS clones was normally sorted and maturated in lysosomes. In KDEL clones, pro-cathepsin D was mostly retained in the ER or partially secreted by high-producer clones but was not maturated. While overexpressed cathepsin D increased experimental metastasis in athymic mice, the pro-cathepsin/D-KDEL was totally ineffective. Moreover, the effect of cathepsin D on metastasis did not seem to be due to saturation of the mannose-6-phosphate receptor since the secretion of two other rat lysosomal enzymes was unaffected by cathepsin D overexpression. We conclude that pro-cathepsin D overexpression facilitates tumor metastasis only when maturated into an active enzyme.
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PMID:Cathepsin D maturation and its stimulatory effect on metastasis are prevented by addition of KDEL retention signal. 813 16


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