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)

Clinical and histopathological features do not reliably distinguish between benign and malignant pheochromocytomas. Additional markers that might be useful prognostic indicators in the pathological assessment of these tumors are sought. Immunohistochemical expression of MIB-1, Bcl-2, cathepsin B, cathepsin D, basic fibroblast growth factor (bFGF), c-met, and type IV collagenase were studied on formalin-fixed tissue from 33 nonconsecutive cases of pheochromocytoma, selected on the basis of reliable long-term follow-up, to determine associations with malignancy. The study group included 33 patients, 19 men and 14 women, with a mean age of 45 years, including five cases of neurofibromatosis (NF), three familial, and one MEN IIb. Mean follow-up was 63.2 months. Ten patients were determined to have malignant pheochromocytomas by the presence of metastatic disease. Features found to be associated with malignancy included MIB-1 labeling index (5% vs 1%) (P = .0009), male gender (90% vs 43%) (P = .008), extra-adrenal location (40% vs 9%) (P = .03), tumor weight (481 g vs 124 g) (P = .05), and young age (38 years vs 49 years) (P = .05). None of the five cases with NF were malignant (P = .04). S-100 positivity showed a significant (P = .02) but nonlinear association with benign tumors. Absent S-100 correlated with greater tumor weight. Malignancy was not associated with right versus left side or bilaterality, although bilateral tumors were smaller. C-met, bFGF, cathepsin B, cathepsin D, and collagenase were strongly expressed in most tumors and were not predictive of outcome, nor was bcl-2, which was variably expressed. Using multiple logistic regression with malignancy as the dependent variable, MIB-1 continued to show a significant association with malignancy (P = .005) independent of any association with sex, age, or extra-adrenal location. Using a cutoff value of MIB-1 labeling of greater than 3% yielded a specificity of 100% and a sensitivity of 50% in predicting malignancy.
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PMID:Prognostic markers in pheochromocytoma. 1020 74

Purpose of our study was to develop a reliable model to define clinical stage I nonseminomatous germ cell tumors (NSGCT) being at low risk and at high risk for occult retroperitoneal metastases based on pathohistological and immunohistochemical parameters in order to stratify the therapeutic approach. 3-5 paraffin-embedded formalin fixed tissue blocks of 149 clinical stage I NSGCT were available from all patients and were analyzed for histopathological features associated with pathological stage: presence/absence of vascular invasion, presence/absence of tunical invasion, percentage of each histological cell type present in the primary tumor. Immunohistochemical expression of MIB-1, p53, bcl-2, cathepsin D and e-cadherin was evaluated using a semiquantitative scoring ystem. Statistical analysis was performed by univariate and multivariate logistic regression models. Percentage of embryonal carcinoma [%EC (p < 0.001)] and presence of vascular invasion [VI (p < 0.0001)] were the most significant independent risk factors associated with pathological stage II disease. Combination of %EC and VI allowed correct prediction of final pathological stage in 88% of patients. Cut-off values including both variables identified correct pathological stage in 131/149 patients (88%). Less than 45% EC and absence of VI correctly identified pathological stage I disease in 91.5%; more than 80% EC and presence of VI correctly predicted pathological stage II in 88% of the patients. %EC and presence/absence of VI appear to be reliable prognosticators to identify both patients at high risk and at low risk for occult retroperitoneal disease. P53, bcl-2, MIB-1, cathepsin D and e-cadherin did not appear to be of prognostic value in clinical stage I NSGCT.
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PMID:[Histopathologic and biological prognostic factors of clinical stage I non-seminomatous germ cell tumors. Implications for risk-adjusted therapy]. 1023 39

The presence of axillary lymph node metastases (ALNMs) is the most important prognostic factor in breast carcinoma. If ALNMs were predictable without performing axillary lymph node dissection (ALND), this procedure would not be necessary in selected patients. Using a combination of some of the new biological markers with the classical ones, our objective was I) to identify the best set of predictors of ALNMs, and II) to define predictive models with either high or low probability of ALNMs. We studied 102 patients with invasive breast carcinoma. All patients underwent ALND, and at least 10 axillary lymph nodes per case were obtained. In the primary tumour we evaluated size, histological subtype and grade, lymphatic/vascular invasion and margin. Hormone receptor status, MIB1 index, microvessel density, c-erbB-2 and cathepsin D expression were assessed by immunohistochemistry, and DNA ploidy and S-phase by flow cytometry. Risk factors for ALNMs were estimated by nonlinear logistic regression analysis. The best predictors of ALNMs were: tumour size > 2 cm [OR 6.45, 95% confidence interval (CI) 21.74 to 1.91], presence of lymphatic/vascular invasion [OR 4.95, CI (14.50 to 1.69)], infiltrative margin [OR 9.87 CI (37.44 to 2.60)] and high MIB-1 index [OR 8.39, CI (33.47 to 2.10)]. Two subsets had a very high risk of ALNMs: I) tumour size > 2 cm, with lymphatic/vascular invasion and infiltrative margin; 26 (89.66%) of 29 patients of this subgroup had ALNMs, and (II) tumour size > 2 cm, with lymphatic/vascular and high MIB1 index.; eight of the nine (89%) patients of this subgroup had ALNMs. We could also identify a two-variable model with a very low risk of ALNMs constituted by tumour with circumscribed margin and low MIB-1 index. Of the 19 patients showing these features, only 1 (5.26%) had ALNMs. Therefore, pathological features of the primary tumour can help to assess the risk for ALNM in invasive breast carcinoma. Such risk assessment might avoid regional surgical overtreatment.
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PMID:Predictors of axillary lymph node metastases in patients with invasive breast carcinoma by a combination of classical and biological prognostic factors. 1050 81

We retrospectively studied the expression of cathepsin D by immunohistochemical analysis in 86 meningiomas (World Health Organization [WHO] grade I, n = 44; WHO grade II, n = 21; WHO grade III, n = 21) and correlated the results with tumor grade and outcome. Staining was scored semiquantitatively based on distribution among neoplastic cells as follows: 0, no staining; 1+, 5% or less of the cells; 2+, 6% to 20%; 3+, 21% to 50%; and 4+, more than 50% of the cells. Cathepsin D expression was observed as follows: 0, 10 cases (12%); 1+, 25 cases (29%); 2+, 15 cases (17%); 3+, 12 cases (14%); and 4+, 24 cases (28%). A higher degree of cathepsin D immunostaining was associated with low tumor grade (P = .0014), low mitotic count (P < .0001), low apoptotic count (P < .0001), and the development of recurrence (P = .035). There was no correlation with outcome or MIB-1 proliferation index. Cathepsin D expression by immunohistochemical analysis was identified in the majority (88% [76/86]) of meningiomas studied. A greater degree of immunoreactivity was observed in the WHO grade I group.
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PMID:Immunohistochemical expression of cathepsin D in meningiomas. 1252 Jul 7

Lipofuscin, known as the "wear and tear" pigment, is seen in cells undergoing regressive changes, the seminal vesicles and the ejaculatory ducts. It is also present in prostatic adenocarcinoma. The purpose of this study is to evaluate the prognostic significance of lipofuscin in prostatic adenocarcinoma. Lipofuscin was evaluated in 736 hematoxylin-eosin-stained slides from 60 conventional and whole-mounted consecutive radical prostatectomies from December 1996 to February 2002. The adenocarcinoma cases were divided into lipofuscin-positive group and lipofuscin-negative group. The Gleason score and pathologic stage were compared between the 2 groups. Percentage of cells positive for p53 and MIB-1 was also compared. Lipofuscin pigment was found in 17 (31%) of 60 prostatic adenocarcinomas as random, sparse, fine, yellow-brown intracytoplasmic granules staining positive for cathepsin D and negative for S-100 protein. Using logistic regression to exclude age as a confounding factor, lower Gleason scores and pathologic stages were demonstrated in the lipofuscin-positive group. There was also a significant difference between the 2 groups in tumor volume, degree of capsular invasion, and positive margins. The difference in seminal vesicle invasion and vascular invasion between the 2 groups was not statistically significant. Lipofuscin in prostatic adenocarcinoma correlates with both lower Gleason score and pathologic stage. Lipofuscin probably indicates slow cellular turnover as suggested by the low proliferation rate and p53 expression. The value of lipofuscin in biopsy as a predictor separating aggressive from indolent disease needs further investigation.
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PMID:Lipofuscin pigment can be used as a prognostic marker in prostatic adenocarcinoma. 1697 16

VLA, expression was immunohistochemically investigated in 145 breast carcinomas. Frozen tissue sections were probed with monoclonal anti-VLA, using automated (Ventana ES 320 system) and quantitative (SAMBA 2005 image processor) immunoperoxidase. A positive anti-VLA, immunoreaction was observed in 86 tumors (23.5%) within epithelial cells of carcinomas. The positive surface in tumors varied from 3% to 38% (mean = 13.8%, SD=11.5) and was independent of the tumor size, grade, type and aneuploidy, and of nodal status. VLA(2) was significantly correlated with VCAM (p<0.01), VLA(2) (p<0.01), E cadherin (p=0.025), and CD44 v (p<0.01), and an inverse relationship was observed with Ki67/MIB 1 (p=0.0024) and P-53 (p=0.034). In contrast VLA, expression proved to be independent of Bcl-2, c-erbB-2, cathepsin D, tenascin, CD31, ELAM, RE, RP, PS2 immunohistochemical expression. The results suggest that VLA, expression in tumors is related to the regulation of other adhesion molecules involved in the metastasis process, but the prognostic significance and clinical relevance of VLA, immunodetection in breast carcinomas remain to be demonstrated.
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PMID:VLA(3)/integrin expression in breast carcinomas evaluated by automated and quantitative immunohistochemistry. 2152 84

Brain-invasive meningiomas have an adverse prognosis, so it is important to detect and correctly evaluate brain invasion by light microscopy. Furthermore, the underlying biological mechanisms responsible for brain-invasive growth are incompletely understood. The primary aim of this study was to identify immunohistochemical markers that could improve identification and evaluation of brain invasion in meningiomas. A second aim was to investigate the process of brain invasion using immunohistochemical markers of proliferation, extracellular matrix modulation, and cell adhesion. From a series of 196 human meningiomas, 67 cases were selected for analysis because of the presence of brain tissue in tumor specimens. Fourteen of these 67 meningiomas were brain-invasive. Invasiveness was determined primarily by evaluation of hematoxylin-erytrosin-saffron- (HES-) stained specimens, although glial fibrillary acidic protein (GFAP), anti-collagen IV, and cluster of differentiation 44 (CD44) markers provided additional information. It was important to examine microscopic sections from various levels of the paraffin-embedded tissue block to adequately assess invasiveness. Sections stained using antibodies against Ki-67/MIB-1, phospohistone-H3 (PHH3), matrix metalloproteinase-9 (MMP-9), cathepsin D, plasminogen activator inhibitor-1 (PAI-1), and E-cadherin antigens were used to characterize brain-invasive meningiomas and to investigate the process of brain invasion. Only increased expression of the extracellular matrix modulator MMP-9 correlated with brain-invasive growth (p=0.025). Examination of HES-stained sections identified brain invasion. Use of relevant immunohistochemical markers did not contribute substantially to this evaluation. Evaluation of stepwise sections should be considered when brain-invasive growth is suspected. MMP-9 may be an important mediator of brain-invasive growth.
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PMID:Immunohistochemical characterization of brain-invasive meningiomas. 2540 Aug 18