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)

Cytosol of primary breast cancers from 217 women of predominantly Arab ethnicity were assayed for uPA, tPA, PAI-1 and a subset for ER, PR and pS2. Serum levels of CEA and CA153 were determined during follow-up. Only tPA correlated to nodal status and tumour grade, and PAI-1 to clinical stage. PAI-1 was related to uPA and both were inversely correlated with PR and pS2 (PAI-1 also to ER). Conversely tPA was directly correlated with ER, PR and pS2. Women with high tumour uPA and PAI-1, but not tPA, had shorter overall, and relapse-free, survival. Only nodal status and clinical stage were independent predictors in multivariate analysis. However, uPA and PAI-1 were more prognostically informative than ER or PR and their usefulness may extend to delineation of patients likely to respond to adjuvant therapy.
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PMID:Clinical implications of urokinase and tissue type plasminogen activators and their inhibitor (PAI-1) in breast cancer tissue. 1195 44

The adhesive glycophosphoprotein (OPN) is capable of inducing metastasis in rodent models ofbreast cancer. We now show that a monoclonal antibody to rat OPN recognizes specifically human OPN using Western blotting techniques andused it to assess the prognostic significance of OPN in primary tumors of a group of 333 patients treated between 1976 and 1982 for operable stage I and stage II breast cancer. The antibody stains immunocytochemically normal breast tissue weakly but pregnant/lactating tissue and 66% of the carcinomas strongly, leaving the remaining 34% as negatively stained. In addition to the carcinoma cells, some host reactive stromal cells, macrophages, lymphocytes, and blood vessels are also stained, but these have been excluded in the following analyses. There is a significant association of staining of carcinomas for OPN with some tumor variables reported previously to be associated with patient outcome: high histological grade (P = 0.024), staining for c-erbB-3 (P < 0.001), p53 (P = 0.014), pS2 (P = 0.025), and borderline significance for progesterone receptor (P = 0.089). The association of staining for OPN with survival times of the patients has been evaluated using life tables over 14-20 years of follow-up (mean 16 years) and analyzed using generalized Wilcoxon statistics. Of the patients who have been classified as OPN-negative, 94% are alive, but only 26% of those classified as OPN-positive are alive after 19 years of follow-up. This association is highly significant (P < 0.0001); the former have a median survival of >228 months and the latter 68 months. When the patients are divided into separate classes based on the percentage of carcinoma cells staining for OPN, the five classes show a progressive decrease in survival with increasing percentage of stained carcinoma cells, and this association is also highly significant (P < 0.0001). Other tumor variables that show a significant association with patient survival times in this group of patients include nodal status, tumor size, histological grade, staining for c-erbB-2, estrogen receptor alpha, or p53. Analysis of the association of patients with carcinomas staining for OPN and their survival in subgroups defined by these tumor variables shows that positive staining for OPN in each subgroup is associated with poorer survival. There is little difference in patient survival times in the OPN-negative group of patients with or without any of the other tumor variables examined. Multivariate regression analysis for 202 patients shows that staining for OPN is most highly correlated with patients' deaths (P < 0.0001), but involved lymph nodes (P = 0.0007), fixed tumors (P = 0.0008), and staining for estrogen receptor alpha (P = 0.008) are also significant independent prognostic variables with that for c-erbB-2 being of borderline significance (P = 0.060). These results suggest that in this group of patients, the presence of the metastasis-associated protein OPN is tightly correlated with patient demise.
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PMID:Prognostic significance of the metastasis-associated protein osteopontin in human breast cancer. 1206 84

To study the behavior and possible correlations of neuron-specific enolase (NSE) with other clinicobiological parameters, we measured the cytosolic levels of this marker by means of an immunoradiometric assay (IRMA) in 95 squamous cell lung carcinoma samples. We also analyzed the levels of pS2, tissue-type plasminogen activator (t-PA), hyaluronic acid (HA), free beta subunit of human chorionic gonadotropin (beta-HCG), CYFRA 21.1 and CA 125 in cytosol. On the cell surface we analyzed the concentrations of epidermal growth factor receptor (EGFR), HA, erbB-2 oncoprotein, CD44s, CD44v5 and CD44v6. Other parameters considered were clinical stage, lymph node involvement, histological grade (HG), ploidy and the cellular S-phase fraction measured by flow cytometry on nuclei obtained from fresh tissues. In the 95 squamous cell carcinomas the cytosolic levels of NSE varied from 4.5 to 2235 ng/mg protein (median: 267) and were significantly higher (p < 0.001) than those observed in 38 samples of normal pulmonary tissue obtained from the same patients (range: 56-657; median: 141.5). When classifying tumors according to the different parameters analyzed, we observed that the levels of NSE were higher in aneuploid than in diploid cases (p = 0.046) and in those that were HG3 than in those that were HG2 (p < 0.001). Tumors with high NSE levels (> 422 ng/mg protein; 75th percentile) were more likely to have high S-phase values (p = 0.012) and were more frequently aneuploid (p = 0.038) and HG3 (p < 0.001) than those with low levels of NSE (< 180 ng/mg protein; 25th percentile). These results lead us to the following conclusions: 1) the cytosolic concentrations of NSE are significantly higher in squamous cell carcinomas than in healthy pulmonary tissue, and 2) the cytosolic concentrations of NSE are not correlated with clinical stage or nodal involvement. However, in our study higher levels of the enzyme were statistically correlated with aneuploidy, histological grade 3 and S-phase. This may explain its association with poorer outcome and progression, but also the more favorable response of tumors with elevated NSE to chemotherapy, as suggested by other groups.
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PMID:Cytosolic levels of neuron-specific enolase in squamous cell carcinomas of the lung. 1453 89

We conducted an analysis on 41 cases of male breast cancer (median age 54 y; range 25-82 y) in Kuwait. Most (51%) were stage II cancers with 65% arising in the left breast. There were 5 (12%) T1 tumours, 23 (56%) T2 tumours and 13 (32%) T3/T4 tumours. They were mostly (95%) infiltrating ductal carcinomas; 97% were grade 2 or 3. Axillary lymph node involvement was found in 69%. Estimated 5-year survival rates were 67% and 58% for overall and relapse free survival respectively. Favourable prognosis was associated with age below 50y, clinical stage I and II, small tumour size (T1, T2), low tumour grade and absence of nodal involvement or distant metastases; nodal status and grade were independent factors for relapse free survival in multivariate analysis. In 18 cases, an immunohistochemical study showed some degree of tumour antigen reaction for ER in 89% of cases, PR in 61%, pS2 in 44%, CathD in 72%, p53 in 56%, c-erbB-2 in 50%, Ki67 and PCNA in 100% and bcl-2 in 78%. There were significant associations between several of these factors but none influenced survival. Despite the high incidence of staining of ER, our data do not support the concept of an endocrine pathway that could be usefully antagonized with antioestrogens for therapeutic benefit, as in women.
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PMID:Evaluation of prognostic factors in male breast cancer. 1496 80

pS2 or TFF1 is a member of the trefoil factor family, which is distributed throughout the gastrointestinal tract in both normal and diseased tissues. It is also considered to be one of the major estrogen-regulated proteins and an indicator of estrogen receptor (ER) functionality. pS2 has previously been investigated in benign and malignant prostate lesions with little information about its relationship to steroid receptor status. Our purpose was to correlate pS2 expression with steroid receptor status (ER alpha and progesterone receptor (PR)) and other pathologic variables in prostate carcinoma. 15 benign prostate hyperplasia (BPH) and 47 prostate carcinoma cases were investigated by means of immunohistochemistry for pS2, ER and PR expression. 80% of BPH showed pS2 cytoplasmic immunoreactivity in hyperplastic acini and about half of these cases also exhibited nuclear staining decorating basal or both basal and luminal nuclei. pS2 was highly expressed in prostate carcinoma (91.4%) with both cytoplasmic and nuclear patterns of staining. The latter pattern was significantly associated with carcinoma having a low Gleason score (p=0.02). pS2 lacked any significant correlation with steroid receptor status, stage or grade. Univariate survival analysis revealed a significant impact of stage (p=0.03) and nodal status (p<0.0001) on patient outcome. The diagnostic value of pS2 expression in prostate carcinoma validated 74.19% accuracy, 91.48% sensitivity and 78.18% positive predictive value. The high sensitivity of pS2 expression in prostate carcinoma could make it a suitable marker for diagnosis of prostate carcinoma, especially in metastatic cases of unknown origin. The absence of correlation and dissimilarity in immunolocalization between pS2 and ER alpha leads to the assumption that ER alpha could not be the regulatory protein for pS2 and may raise questions about the functionality of ER alpha in prostate. The nuclear pattern of pS2 immunoreactivity either in benign or malignant prostatic lesions is similar to the published data on ER beta distribution and could also identify a subset of carcinoma patients with a favorable prognosis.
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PMID:pS2 (TFF1) expression in prostate carcinoma: correlation with steroid receptor status. 1913 93

Previous studies have shown that pS2 and cathepsin D are linked in lymph node positive (N+) tumours, but not in tumours from lymph node negative (N-) patients. The purpose of this study was to understand whether or not size would effect the relationship between pS2 and cathepsin D. Findings were further extended to some subgroups of tumours obtained stratifying for T and N and particularly to the small (TI) but aggressive (N+) cancers (T1/N+) and to those of size greater than 2 cm (T2 and T3) but yet node negative (T2+T3/N-). Oestrogen (ER) and progesterone (PR) receptors, pS2 and cathepsin D concentrations were therefore assayed in 355 primary breast cancers. ER, PR, pS2 and cathepsin D did not correlate to nodal status and size of the tumours; no significant differences in the expression of these four biological factors between infiltrating ductal carcinomas without special features (NOS) and non-NOS carcinomas were found. Multivariate analysis performed among cathepsin D, ER, PR and pS2 indicated that, in T1 tumours, pS2 was the most important variable and the best predictor in cathepsin D determination, while such association was absent in T2 and T3 tumours. pS2 and cathepsin D significantly associated also in tumours obtained from N+ patients, and such correlation was highest in T1 tumours with positive axillary nodes (N+/T1). pS2 and cathepsin D did not associate in tumours taken from N- patients. Considering the NOS carcinomas, correlation between pS2 and cathepsin D in the N+, T1 and N+/T1 subgroups was higher in the poorly differentiated grade 3 with respect to grade 1 and grade 2 cancers. The data suggest that pS2 could have a role in cathepsin D expression and we hypothesise that such control could be an early biological event occurring in the development and progression of particularly aggressive (N+/grade 3), small (T1) breast cancers.
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PMID:Effect of tumor size on the association between ps2 and cathepsin-d in primary breast-cancer. 2155 3

c-myc proto-oncogene amplification seems to have a prognostic value in breast cancer. In this study, quantitative analysis of c-myc amplification was carried out by differential polymerase chain reaction technique (d-PCR) using beta-globin as the reference gene. d-PCR assessment showed coampIification products of c-myc and beta-globin depend on variations in reaction factors such as the genomic DNA concentration, the relative concentrations of the various amplimers, the thermostable DNA polymerase concentration and the number of cycles. However, amplification of c-myc can be estimated quantitatively. In addition, results of individual sets of d-PCR can be expressed on a standard reference scale. A clinical study of 309 patients with breast cancer found c-myc amplification, respectively in 19% (45/236) of primary tumour tissues, 21% (4/19) of subsequent second primary cancers, 36% (4/11) of tumours of patients with bilateral lesions, 40% (8/20) of local recurrence tumours and 22% (5/23) of metastatic lesions. Amplification of c-myc was observed more frequently in histological grades 2-3 (p<0.02), in ER negative (p<0.01) and PgR negative tumours (p<0.02), but was not associated with age, tumour size, nodal status, histology, cytosolic cathepsin D or pS2. d-PCR appears amenable to automation and should facilitate large scale, inter laboratory gene amplification studies.
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PMID:Analysis of C-myc amplification by the differential polymerase chain-reaction (d-PCR), study in breast-cancer. 2160 66

Breast cancer (BC) is the most common cancer in women and the second leading cause of their cancer death. Establishing an accurate BC prognosis is very difficult because of its heterogeneity. Elevated TFF1 levels in serum were associated with development of BC, TFF1 expression was upregulated in BC compared to the healthy breast tissue. The aim of this study was to investigate the function of TFF1 in BCs, and to assess whether serum TFF1 could be used in formulating a prognosis for BC patients. In silico analyses were carried out to determine the expression of TFF1 mRNA in different types of BC and the association between TFF1 expression and survival of BC patients. Expression of TFF1 protein was checked in 52 paraffin-embedded tissues of BCs by immunochemistry, and serum concentration of TFF1 in 70 BC patients and 32 healthy controls was measured by ELISA. Functional activities of TFF1 in BC cells were determined by CCK-8 assay, colony formation, BrdU-DNA synthesis, and assays for migration and invasion. Results showed that expression of TFF1 mRNA was correlated with expression of biomarkers of luminal cancers including ESR1, GATA3, FOXA1, MYB and XBP1. In addition, patients with ER+BC had higher expression of TFF1 than those with ER- (p < 0.05). There was also lower expression of TFF1 in triple-negative breast cancer (TNBC) than in non-TNBC (p < 0.05), which corresponds with the level of serum TFF1 in TNBC patients, compared with non-TNBC patients (p < 0.001). Furthermore, expression of TFF1 was associated with tumor size (p = 0.002), nodal status (p < 0.001), histological grade (p < 0.001), ER status (p = 0.012), PR status (p < 0.001) and HER2 (p < 0.001), while serum TFF1 was only statistically different among BC with ER+, PR + and HER2+ (p = 0.04139, 0.0018, 0.0004). Elevated TFF1 expression correlated with increased overall survival of BC patients (p = 0.00068). Finally, TFF1 was found to inhibit the cell growth, colony formation, migration and invasion of BC cells in vitro. All these results suggest that expression of TFF1 was related to ER status of BC and that expression of TFF1 was lower in TNBC than in non-TNBC. TFF1 was found to inhibit proliferation, migration and invasion of BC cells in vitro. Expression of TFF1 was associated with clinical characters of patients with BC. Serum TFF1 could be used to predict prognosis of patients with BC, especially non-TNBC.
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PMID:Trefoil factor 1 (TFF1) is a potential prognostic biomarker with functional significance in breast cancers. 3198 8


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