Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Within the past few years, the measurement of serum and tissue markers, especially the latter, has assumed a more significant role influencing clinical decisions about treatment and follow-up of patients with malignant disease. Breast cancer is a useful paradigm to illustrate the types and importance of these various markers. Tissue markers, including nuclear grade, steroid hormone receptors, DNA index, ploidy, expression of oncogenes or tumor-suppressor genes, epidermal growth factors, cathepsin D, proliferating cell nuclear antigen (PCNA), Ki-67, p32, and others, may influence choices of initial treatment as well as adjuvant chemotherapy and (or) hormone administration. The serial measurement of serum markers, those currently available and those on the horizon, for example, may offer a way to monitor patients at risk for recurrent cancer. Although the current role of these markers may be controversial, as information about them is collected and refined, in the future perhaps a panel of such studies could be incorporated into forthcoming clinical staging systems for carcinoma of the breast and other malignancies to define both treatment and outcome.
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PMID:Clinical applications of serum and tissue markers in malignant disease: breast cancer as the paradigm. 822 51

Male breast cancer is probably hormone dependent, but studies are few due to the rarity of this tumor. We have studied 21 cases of male breast cancer immunohistologically for estrogen receptor (ER) and cathepsin D (CD) expression. In carcinoma of the female breast ER expression is associated with longer patient survival and responsiveness to hormonal manipulation. Cathepsin D is an estrogen-regulated lysosomal protease with proteolytic and mitogenic properties whose presence denotes a functioning ER. In our series of male breast carcinomas 86% were ER positive and 62% were CD positive; this compares with typical figures of 50% and 66%, respectively, for female breast cancer. We observed no trends between expression of ER and CD and patient survival; immunostaining for ER and CD is unlikely to be clinically useful in carcinoma of the male breast. The high rate of ER positivity in males suggests that male and female breast carcinomas are biologically different tumors.
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PMID:Expression of cathepsin D and estrogen receptor in male breast carcinoma. 838 63

A series of 30 cases of male breast cancer in the North-East of Scotland is reviewed. The aims of the study were to document clinico-pathological and immunocytochemical features (available for 25) of these patients and to establish which factors could predict prognosis. Tumours were studied for the expression of oestrogen receptors (ERs), the oestrogen-dependent proteins pS2 and cathepsin D, the oncoprotein products of c-erb-B2 and the p53 tumour-suppressor-gene derived protein. Clinico-pathological features documented were in agreement with those reported by other authors. The overall 5-year survival was 53%. Tumour grade and lymph-node status influenced prognosis. In this series, 64% of the tumours expressed ERs, 50% pS2, 46% cathepsin D, 42% the c-erb-B2 transmembrane oncoprotein and 54% p53. In contrast to female breast cancer, the presence of either substantial amounts of ERs or the oestrogen-dependent protein pS2 correlated with poorer prognosis in males. This correlation has not previously been documented.
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PMID:Male breast cancer: clinico-pathological features, immunocytochemical characteristics and prognosis. 884 66

There is ample information on the clinical role of biologic factors in female breast cancer: urokinase-type plasminogen activator (uPA), its receptor uPAR, its inhibitors PAI-1 and PAI-2, cathepsin D and pS2-protein. However such reports are missing or very rare for male breast cancer. We determined the cytosolic levels of oestrogen receptor (ER), progesterone receptor (PgR), cathepsin D, pS2-protein, uPA, uPAR, PAI-1 and PAI-2 of the primary tumour tissues from 40 male breast cancer patients. The tumour levels were compared with those of 180 matched females and 4114 historic females with breast cancer. In male breast tumours the level of PgR was higher, those of uPA, PAI-1, PAI-2 and cathepsin D lower. The tumour level of ER in men was similar to those in the matched and postmenopausal women, but much higher than those in the historic women. Male breast cancer seems to be biologically different from female breast cancer. Correlation of the eight cell biologic factors with disease outcome showed that PAI-1 (p = 0.03) was the only independent predictive factor for poor prognosis in male breast cancer.
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PMID:Clinical relevance of biologic factors in male breast cancer. 1172 61

56 cases of infiltrating duct carcinoma of the breast were studied for the expression of cathepsin D and topoisomerase II alpha. The results were correlated with the morphological differentiation, as determined by the Nottingham's modification of the Bloom-Richardson system. Cathepsin D posltivity in tumour cells and stromal cells was seen in 44.6% and 55.4% cases respectively, whereas topoisomerase II alpha positivity was seen in 33.9% cases. In grade II tumours cathepsin D in tumour cells and stromal cells was 44.4% and 47.2% respectively, as compared to 27.8% posltivity for topoisomerase II alpha. The corresponding figures for grade III tumours were 50.0%, 79.6% and 64.3 % respectively. As grade I comprised only 3 cases no statistical correlation could be observed. It is evident that with increase in tumour grade there is a statistical increase in expression of cathepsin D, a lysosomal acidle protease-implicated in the process of tumour invasion and metastasis, and of topoisomerase II alpha, a marker of rapid cell proliferation and aneuploidy.
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PMID:CORRELATIONSHIP OF CATHEPSIN D AND TOPOISOMERASE II ALPHA WITH NUCLEAR GRADING IN BREAST CANCERS. 2740 60