Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04155 (pS2)
 1,234 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two new immunoenzymatic assays for c-erbB-2 oncoprotein and epidermal growth factor receptor (EGF-R) (Oncogene Science) in human breast cancer were validated. Correlations between these assays and some clinical and biological parameters were also studied. The repeatability and reproducibility of standard curves for the two methods gave a coefficient of variation (CV) of less than 4% and about 10% respectively. The accuracy of c-erbB-2 oncoprotein and EGF-R assays was examined by using dilution and recovery tests throughout the standard curves. The linear relations between theoretical and measured values, for these tests, had slopes close to 1 and an intercept near 0. The median value for EGF-R, measured on solubilized membranes of 290 primary tumors, was 0.12 fmol/micrograms protein, the mean value was 0.37 (range 0 to 35.7). For c-erbB-2 oncoprotein, the median value, measured using the same population, was 2.75 human neu unit/micrograms protein, the mean value was 7.85 (range 1 to 125). There was an inverse relationship between EGF-R values and those for the estrogen receptor (ER), progesterone receptor and pS2 protein as well as menopausal status. C-erbB-2 oncoprotein concentrations were positively correlated with ER, pS2 protein and cathepsin D. Furthermore, a significant positive correlation was observed between EGF-R levels and c-erbB-2 oncoprotein levels. In conclusion, immunoenzymatic assays of EGF-R and c-erbB-2 oncoprotein are easy to use, sensitive and reliable. The accurate standardisation of immunoenzymatic assays could contribute to the clinical use of EGF-R and c-erbB-2 oncoprotein as prognostic factors in breast cancer.
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PMID:[Immunoenzymatic assays of c-erbB-2 oncoprotein and epidermal growth factor receptor in breast cancer: correlation with clinical and biological parameters]. 888 58

The present study attempts to clarify the specific contribution of cathepsin D (CD) and pS2 to the progression of breast cancer (BC) by examining the relationship between these two factors and TNM status, tumour grade, estradiol receptors (ER) and the prognosis factors epidermal growth factor receptor (EGFR) and neu amplification in a group of 270 BC patients. CD and pS2 were determined by an immunoradiometric procedure in tumour cytosols obtained for ER. Neu amplifications were evaluated by dot-blot, in tumour DNA. EGFR was determined in membrane tumour preparations obtained from ER cytosols by a two-point radiometric saturation assay. CD is basically related to bad prognosis factors and has a direct correlation with tumour size (P = 0.025) and EGFR content (P = 0.007) and is associated with the presence of metastases (P = 0.000). pS2 is mostly related to good prognosis factors and showed an inverse correlation with the Scarff-Bloom Index (P = 0.011) and a direct correlation with ER content (P = 0.014). Finally, pS2 and CD also showed a strong mutual association (P = 0.009) and the fact that both correlated with ER content confirms in tumours the experimental finding that they are estrogen-induced proteins.
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PMID:Specific oncological contribution of cathepsin D and pS2 in human breast cancer: their relationship with TNM status, estradiol receptors, epidermal growth factor receptor and neu amplification. 892 Feb 30

CD44 variants carrying sequences encoded by exon v6 are preferentially expressed in metastatic animal cancer cell lines. CD44v6 overexpression correlates tumor dedifferentiation and progression in some human carcinomas, but the relationship of CD44v6 overexpression with metastatic behavior of tumor observed in animal models is controversial, particularly in breast carcinomas. The discrepancies probably result from analytical bias. We investigated CD44v6 and CD44s expression in 218 frozen samples of primary breast carcinomas. Immunocytochemical procedure was performed under optimal technical conditions using commercially available 2F-10 monoclonal antibody (MAb), a microprocessor-controlled automated device (Ventana Medical Systems, Tucson, AZ), and quantitative evaluation of results by processing digitized-colored microscopic images (SAMBA, Grenoble, France). CD44v6 expression in tissue sections was shown to be independent of the patient age, tumor size, histological types and grades, and the lymph node status. CD44v6 expression was also independent of the expression of molecules endowed with poor prognostic significance detected by MAbs (anti-p53, anti-c-erb B-2 protein, MIB1) on consecutive sections. No significant relationship could be evidenced either between CD44v6 expression, and CD31 involved stromal angiogenesis and cathepsin D. Finally, CD44v6 was independent of markers of hormone dependence (estrogen and progesterone receptors, pS2) and of multidrug resistance (P-glycoprotein). Similar results were observed with anti-CD44s. We conclude that the true prognostic significance of CD44v6 overexpression still remains to be shown under rigorous technical conditions (frozen samples, well-documented MAbs, and optimal standardization of procedure using automation and quantitative analysis) providing data appropriate for further correlation with long-term patient follow-up.
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PMID:Automated and quantitative immunocytochemical assays of CD44v6 in breast carcinomas. 904 92

The total cellular p185(HER-2/neu) protein (p185) content was measured by ELISA in 346 invasive primary breast cancers, and the results were compared with those of estrogen (ER) and progesterone (PR) receptors, pS2 and Cathepsin D (Cat D) content. At a cut-off level of 260 fmol/mg protein, 53 of the 346 tumors (15%) were p185-positive. A significant positive correlation was observed between p185 levels and those of Cat D, and a weaker, though significant, positive correlation with ER, and pS2 levels, but not with those of PR. However, when only the 293 p185-negative tumors were considered, the correlation between p185 and ER improved substantially, and statistical significance was reached for PR. p185-positive tumors exhibited lower ER and PR content and higher Cat D content than p185-negative tumors. The pS2 content, in contrast, did not undergo significant variation. Tumors considered to be p185-positive were significantly more frequently positive for Cat D at the cut-off of 45 pmol/mg protein, and were more frequently negative for ER and/or PR, but only significant at the cut-off of 15 fmol/mg or higher for both steroid receptors. Finally, p185 status was not associated with menopausal status, tumor size, axillary-lymph-node invasiveness or distant metastases. These results suggest that 260 fmol/mg protein as the cut-off for p185 allows the identification of a tumoral sub-population with a more aggresive phenotype.
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PMID:Quantitative analysis of p185(HER-2/neu) protein in breast cancer and its association with other prognostic factors. 913 51

Glutathione S-transferases mu (GSTM) are dimeric cytosolic isoenzymes. They catalyze glutathione conjugation upon a large variety of electrophiles as carcinogens, trans-stilbene peroxide or benzo(a)pyrene. The gene GSTM1 is localized on chromosome 1p13, it has drawn attention because it is absent approximately in 50% of the white population. GSTM1 null genotype seems linked with susceptibility to cancers as lung, colon and bladder cancers. We have studied GSTM1 genotype from 373 primary breast tumours. The GSTM1 null genotype was found in 50% of the cases (185/373). The incidence study of GSTM1 copy number on clinical and biological variables displayed a significant difference (p < 0.01) of the GSTM1 genotype, showed by the tumour, according to the patient age at diagnosis. The patients younger than 55 years had a percentage more important of primary tumours (65%) with a copy number of GSTM1 gene, inferior or equal at one, compared to the patients older than 55 years (52%). The tumours, whose cathepsin D level was high, presented few copies of GSTM1 gene (p < 0.03). There was no other relationship, particularly, with tumour size, node status, histological type, hormonal receptors, pS2 cytosolic level GSTM1 gene seems protect the mammary gland from cancerogenesis with its detoxification role. This results had not, pointed out in breast cancer, yet.
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PMID:[Glutathione S-transferase mu 1 (GSTM1): susceptibility gene of breast cancer]. 918 Aug 57

Expression of the bcl-2 gene was investigated in 218 human breast carcinomas by immunohistochemical analysis. Immunodetections were assessed using (1) frozen sections, (2) documented commercially available monoclonal antibody (bcl-2/124, Dako), (3) automation of immunoperoxidase technique (Ventana) and (4) quantitative evaluation of results by image analysis (SAMBA) and statistical analysis of quantitative data (BMDP software). Bcl-2 protein expression was correlated with current prognostic indicators and with molecular markers detected by the same procedure as for Bcl-2. It was shown that Bcl-2 expression is not related to patients' age, tumour size and type or lymph node status, but an inverse relationship was observed between Bcl-2 and tumour grade (P < 0.0001). An inverse relationship was also observed between Bcl-2 expression and p53 (P < 0.0001), Ki67/MIB1 antigen- (P = 0.0012), and P-gp- (P = 0.002) positive immunoreactions. In contrast, anti-Bcl-2 positive reaction was significantly associated with ER-positive (P < 0.001) and with ER/PR-positive or ER/PR/pS2-positive immunoreactions (P < or = 0.005). Bcl-2 expression was independent of CD31 and cathepsin D expression. Thus, Bcl-2 protein, thought to be antiapoptotic, exhibits parodoxical expression in human breast carcinomas. It is strongly detected in low-grade tumours (well-differentiated) with low (MIB1) growth fraction, but is independent of the tumour progression (size, node status, CD31, and cathepsin D). Bcl-2 acting on apoptosis is related to p53 gene abnormalities in breast carcinomas. Bcl-2 protein expression may also be involved in response to endocrine therapy (associated to ER/PR/pS2 positive immunoreactions) and probably with chemoresistance mechanisms (inverse relationship with P-gp).
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PMID:Automated and quantitative immunocytochemical assays of Bcl-2 protein in breast carcinomas. 925 1

In this study the unexpected findings from the analysis of 278 breast cancer tissue specimens are reported. A surprising strongly positive correlation between an unfavourable and a favourable prognosis with markers cathepsin D and pS2 respectively, was revealed by linear regression analysis (Pearson, Student-T-Test). In the relevant literature reviewed only one similar, although indirect, observation was found. On the other hand, a weak relationship between pS2 and ER has emerged using the same method, while the pS2/PgR association remained strong. The latter supports the hypothesis that pS2 positivity is associated with positive PgR and may be a marker of functioning ER, irrespective of ER status. These and other similar findings underline the need for a better understanding of the underlying molecular events as well as the necessity of an effective prognostic evaluation model for breast cancer.
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PMID:Relationships between cathepsin-D, pS2 protein and hormonal receptors in breast cancer cytosols: inconsistency with their established prognostic significance. 941 20

The evaluation of prognostic factors for breast cancers is important for therapeutic decisions both at the time of surgery and during postoperative surveillance. Cathepsin-D (cath-D) is an estrogen inducible aspartyl protease. Studies have demonstrated two biological activities, at an acidic PH, of the protein: a mitogenic and a proteolytic activity; both the growth promoting activity and the extracellular proteolytic activity suggest that cathepsin D (cath-D) may have prognostic significance in breast cancer. Measurement of cath-D in breast tissue, in fact, is highly significant in predicting recurrence as well as disease free interval and overall survival. The pS2 is a small cysteine-rich protein specifically expressed under estrogen transcriptional control. Expression of the pS2 protein in breast carcinoma is a useful guide to prognosis and response to tamoxifen: appropriate adjuvant therapy can be selected on the pS2 status of the tumor; patients with pS2 expression had better overall survival and a longer survival time after the first recurrence than those without pS2 expression. For these reasons, these two new prognostic markers could be suggested as habit factors in breast cancer.
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PMID:Prognostic significance of the estrogen-regulated proteins, cathepsin-D and pS2, in breast cancer. 956 Oct 19

VLA2 is thought to be involved in the metastatic process in malignant tumours, in particular in carcinomatous cell adhesion to vessel basement membrane. VLA2 expression was immunohistochemically investigated in 204 breast carcinomas. Frozen tissue sections were probed with monoclonal anti-VLA2 using automated (Ventana ES 320 System) and quantitative (SAMBA 2005 image processor) immunoperoxidase. A positive anti-VLA2 immunoreaction was observed in 48 tumours (23.5%), within epithelial carcinomatous cells. The VLA2-positive surface in tumours varied from 3% to 20% (mean 8.75, S.D. 7.17) and was correlated with histoprognostic indicators and tumour expression of various antigens detected using the same method as that for VLA2. The results show that VLA2 immunoexpression was independent of the tumour size, grade, type and aneuploidy, and of the nodal status. VLA2 significantly correlated with ELAM, VCAM, VLA3 and P-glycoprotein (P-gp) (P < 0.01) and inversely correlated with cathepsin D (P < 0.001), but was independent of Ki67/MIB1, p53, bcl-2, c-erbB-2, E cadherin, CD44v, CD31, oestrogen and progesterone receptors' (ER, PR) antigenic sites and pS2. The exact role, if any, of VLA2 in tumour cell dissemination remains to be elucidated and the clinical relevance of VLA2 immunodetection in breast carcinomas requires further investigation of the correlation between VLA2 immunocytochemical expression and patients' outcome and response to chemotherapy.
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PMID:VLA2 integrin expression in breast carcinomas evaluated by automated and quantitative immunohistochemistry. 964 45

In spite of the complexity of the biological basis of the hormonal regulation of breast cancer, clinical studies tend to simplify the information by mainly categorizing continuous variables related to hormonal status and not considering the interactions between variables. The present study was planned to examine the presence of an interaction between cathepsin D (Cath-D) and pS2 in patients treated with adjuvant tamoxifen in a homogeneous subset of node-positive postmenopausal patients and to evaluate the contribution of the interaction to the predictive ability of the model. Steroid receptors (ER and PgR) were measured in cytosol using the dextran-coated charcoal method, while Cath-D and pS2 were determined using commercially available immunoradiometric assays. The prognostic role of each variable and their joint effect were investigated using a Cox regression model. Biological variables were analyzed as continuous and when their prognostic relationship did not seem linear, a restricted cubic spline regression smoothing approach was adopted. The logarithm of hazard showed a linear relationship with the log(ER), while it i) remained almost constant up to about 20 fmol/mg and subsequently decreased for PgR; ii) was almost constant up to about 50 pmol/mg and subsequently decreased for Cath-D; iii) decreased for increasing log(value) up to about 33 ng/mg and subsequently increased for pS2. In the multivariate analysis both PgR and the interaction between pS2 and Cath-D retained a significant prognostic role. For low values of pS2, the prognosis worsened with the increase in Cath-D levels and this relationship reversed for high values of pS2. From the results of the present study we can conclude that i) a significant interaction between Cath-D and pS2 was found in this case series; ii) the prognostic relationship should not be underestimated in clinical decision making; iii) a predictive score obtained considering the contribution of PgR, pS2 and Cath-D could be useful for clinical use.
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PMID:Impact of steroid receptors, pS2 and cathepsin D on the outcome of N+ postmenopausal breast cancer patients treated with tamoxifen. 968 Dec 97


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