Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Breast cancer is the most common malignant tumor among women, comprising an estimated 24% of all cancer cases and 18% of all cancer deaths. At least half of the patients with primary breast cancer will ultimately die by metastatic disease. The tumor characteristics, the natural course of the disease and the response to therapy vary strongly. A number of recently detected cell biological parameters such as oncogenes/suppressor genes, growth factors and secretory proteins are more or less important prognostic factors, because they influence the characteristics and behavior of a tumor with respect to metastatic pattern, extent of cellular differentiation, growth rate and response to treatment. However, there is no clear consensus how best to identify patients at high or low risk. In our experience c-myc amplification and pS2 protein are strong prognosticators for relapse rate, while in advanced disease (apart from a negative estrogen/progesterone receptor/pS2 status) amplification of HER2/neu is a good prognosticator for failure to endocrine therapy. In the diagnosis of breast cancer, in vivo imaging of tumors by labeled hormones or other factors also forms a new development which might have implications for treatment too. With respect to treatment both endocrine and chemotherapy can cure a minority of patients with micrometastases, but in patients with advanced disease only a prolongation of (progression-free) survival can be reached. Response rates decrease with increasing tumor load. In the past decade a number of interesting new endocrine agents has been developed such as new (pure) (anti)steroidal agents, vitamins, aromatase inhibitors, analogs of peptide hormones, prolactin inhibitors and growth factor antagonists. However, less is known on the (potential) interaction between hormones, chemotherapeutic agents, retinoids, cytokins, growth factor antagonists and irradiation. Rapid detection of new powerful combination therapies are needed to improve treatment results during the nineties.
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PMID:Clinical breast cancer, new developments in selection and endocrine treatment of patients. 144 97

pS2 protein expression has been reported to have prognostic significance in human breast carcinomas and to correlate with estrogen receptor positivity, although these findings have not been confirmed by all investigators. pS2 positivity was compared to various clinical and histologic parameters in a retrospective study of 290 patients (median follow-up 7.2 years) and significantly correlated with tumor grade and estrogen receptor content (p = 0.001 and p = 0.0007, respectively). Significant associations between pS2 positivity and lymph node metastases, T stage, histologic tumor type, and patient age were not observed. Univariate and multivariate analyses (controlling for estrogen receptor content, T and N stage) of the patient population at large showed that pS2 positivity was not predictive of disease-free or overall survival. Univariate analysis of lymph node negative patients demonstrated that both pS2 and estrogen receptor positivity were significantly associated with a better outcome. Multivariate analysis of these patients, however, showed that only estrogen receptor data had independent prognostic significance. This study suggests that immunohistochemical analysis for pS2 protein expression will not contribute additional prognostic information if the estrogen receptor content is known.
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PMID:pS2 expression in primary breast carcinomas: relationship to clinical and histological features and survival. 162 14

Expression of the oestrogen-regulated pNR-2/pS2 protein has been studied in paraffin sections of a series of 172 primary breast cancers using an immunohistochemical technique. Positive staining of tumour cells was found in 117 tumours (68%): most of these tumours contained only a small proportion of positive cells. pNR-2 immunohistochemical staining correlated positively and significantly with the presence of oestrogen receptor. Mean percentages of pNR-2 positive cells were lower in tumours from postmenopausal women. Smaller, better differentiated tumours were significantly more likely to stain positively for pNR-2. The percentages of pNR-2 positive tumour cells in primary tumours and synchronously excised lymph node metastases were very similar. pNR-2 expression showed an unexpected positive association with lymph node metastasis. We were unable to find any significant association between pNR-2 immunohistochemical staining and either time to relapse or overall survival. There was a significant association between pNR-2 expression in primary tumours and response to endocrine therapy on relapse: positive pNR-2 immunohistochemical staining in primary tumours is predictive of response to hormonal therapy on relapse.
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PMID:pNR-2/pS2 immunohistochemical staining in breast cancer: correlation with prognostic factors and endocrine response. 185 Jun 11

Seventy-two patients with advanced breast carcinoma (42% bone, 25% visceral, 5.5% soft tissue, and 27.5% multiple site metastases) were evaluated to determine the relationship between tumor expression of the estrogen-regulated protein pS2, estrogen receptor (ER) or progesterone receptor (PgR) content, and response to hormonal therapy. Twenty-nine % of tumors were pS2 positive, 64% were ER positive, and 29% were PgR positive. Of the ER-positive patients (n = 43), 15 (35%) had greater than 10% of the invasive carcinoma which immunostained for pS2 (these were considered pS2 positive). Only 3 of 24 ER-negative tumors were pS2 positive. A weak association between pS2 expression and ER content (P = 0.08) but not PgR content was observed. Of pS2-positive patients, 52% had a partial or complete response to hormonal therapy. In 24% of pS2-positive patients the disease stabilized with treatment. In contrast, 27% of pS2-negative patients had a partial or complete response. In 10% of these patients the disease stabilized. Similar associations between therapeutic response and ER or PgR were not observed. The odds of having a clinical response to hormonal therapy was greater for pS2-positive than for ER- or PgR-positive tumors. pS2 expression may define a subset of ER-positive tumors that are more likely to respond to hormonal treatment.
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PMID:pS2 expression and response to hormonal therapy in patients with advanced breast cancer. 198 78

Expression of an estrogen-regulated protein known as the 27,000-d heat-shock or stress-response protein (srp-27) was evaluated in human breast carcinomas and established breast cancer cell lines. Results obtained by Northern and Western blot analyses and immunohistochemical methods were concordant. Immunohistochemical assessment of srp-27 expression in 300 breast carcinomas (with median patient follow-up of 8 years) was performed. Twenty-six percent of lymph node-negative and 45% of lymph node-positive tumors were overexpressors. Univariate analysis demonstrated significant correlations between srp-27 overexpression and estrogen receptor (ER) content, pS2 protein expression, nodal metastases, advanced T stage, lymphatic/vascular invasion, and a shorter disease-free survival period (but not a shorter overall survival) for the study population as a whole. Regression tree analysis showed that srp-27 expression was an independent prognostic indicator for disease-free survival only in patients with one to three positive lymph nodes. The Cox proportional hazards model confirmed the independent prognostic significance of nodal involvement, T stage, and ER content but failed to recognize srp-27 overexpression as a significant independent parameter predictive of patient outcome in the patient population as a whole. The observed associations between srp-27 overexpression and more aggressive tumors suggest a biologic role for srp-27 in human breast carcinomas.
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PMID:Stress response protein (srp-27) determination in primary human breast carcinomas: clinical, histologic, and prognostic correlations. 198 96

For quantificative determination of ERBB2 gene amplification in archival human carcinoma specimens we have developed a rapid, non-radioactive approach, which is based on the differential polymerase chain reaction (PCR) and fluorescent DNA technique. Sequences from the ERBB2 gene and from a single-copy reference gene were amplified simultaneously by PCR, in which one of each primer pair was fluorescently labelled. PCR products were separated by polyacrylamide gel electrophoresis in an automated DNA sequencer and directly quantified after laser activation and emission scanning using appropriate software. This fluorescent differential polymerase chain reaction (fd-PCR) method was used for quantificative determination of ERBB2 gene amplification in 195 formalin-fixed, paraffin-embedded breast carcinoma tissues. ERBB2 gene amplification was found in 52 (26%) of these tumors and correlated significantly with tumor size, absence of estrogen receptor (ER) and pS2 expression, but not with absence of progesterone receptor (PR) or presence of epidermal growth factor receptor (EGF-R) expression, lymph-node metastases or grading. In univariate analysis, ERBB2 gene amplification showed no significant correlation with clinical outcome, either in the whole population or in the subgroup defined by positive axillary lymph-node metastases. However, within the node-negative subgroup, patients with ERBB2 gene amplification had significantly decreased relapse-free survival and overall survival (p < 0.05). The fd-PCR assay is a valuable tool for determination of amplification of ERBB2 gene as well as further oncogenes. In this way, more detailed information about individual tumor biology may be acquired by a routine assay.
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PMID:ERBB2 gene amplification detected by fluorescent differential polymerase chain reaction in paraffin-embedded breast carcinoma tissues. 759 Dec 99

Expression of the pS2 protein in breast carcinoma is a useful guide to prognosis and response to tamoxifen. We have investigated pS2 protein expression in both the primary tumour and lymph node metastases (LNM) using a computer-assisted image analysis system. In a consecutive series of 208 patients undergoing surgical excision of primary breast cancer with axillary clearance, 89 patients were found to have involved lymph nodes. We found a highly significant correlation between pS2 expression in primary tumours and their LNM when 5% was taken as the cut-off for positive staining (Fischer Exact, P < 0.0001). There was also a highly significant correlation between the proportion of positive staining between the local metastases and primary tumours (Spearman's rank order correlation = 0.87; P < 0.0001). We conclude that the pS2 status of LNM can be accurately predicted from the pS2 status of the primary tumour. As such, appropriate adjuvant therapy for primary breast cancer, or second line therapy for disseminated disease can be selected on the pS2 status of the primary tumour alone.
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PMID:Correlation of pS2 expression of involved lymph nodes in relation to primary breast carcinoma. 772 Aug 88

In this study we analysed the cytosolic concentrations of the estrogen-regulated protein pS2 in tumors of 462 breast cancer patients, 16 benign breast tumors and 58 metastases. The median pS2 values were highest in breast cancer, followed by benign tumors and metastases (Kruskal-Wallis Test: p < 0.05). Information on other prognostic factors and clinical outcome was available for 354 patients (median follow-up, 35 months). We found a pS2 value of 2 ng/mg protein to be the best cut-off level to discriminate between pS2+ (63%) and pS2- (37%) tumors with respect to relapse-free survival (RFS) and overall survival (OS). The pS2 status was significantly correlated with age, estrogen receptor (ER) and progesterone receptor (PR) status. pS2 was negatively correlated with grading and was more often positive in invasive lobular than in invasive ductal carcinomas. ER, pS2 and grading were highly significantly correlated with each other. In univariate analysis pS2- patients showed a significantly shorter RFS (p = 0.0001) and OS (p = 0.0005). However, multiple regression analysis revealed that in our series of patients the pS2 status provides no independent prognostic information.
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PMID:pS2 protein status fails to be an independent prognostic factor in an average breast cancer population. 784 May 11

Expression of the hormone-regulated genes, pS2, prolactin-inducible protein (PIP) and fatty acid synthetase (FAS), was investigated by Northern blotting in primary breast carcinoma, metastatic breast cancer in axillary lymph nodes, in uninvolved breast tissue from mastectomies and in normal lymph nodes. There were considerable differences in expression of the genes between the tissues. The proportion of tissues containing PIP-mRNA decreased from uninvolved breast tissue to primary breast carcinoma to metastatic carcinoma. The reverse applied to FAS-mRNA which was found more often in metastatic cancer than in primary cancer, and least frequently in uninvolved breast tissue. Yet another pattern was observed for pS2 expression. The highest proportion of tissues demonstrating gene expression was found in primary breast cancer with both metastatic tumor and uninvolved breast tissue expressing the gene less frequently. pS2-mRNA and PIP-mRNA could only rarely be detected in trace amounts in normal lymph nodes. In contrast, FAS-mRNA was present in about one third of normal lymph nodes. Only pS2-mRNA showed an association with estrogen and progesterone receptor status.
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PMID:Hormone-regulated genes (pS2, PIP, FAS) in breast cancer and nontumoral mammary tissue. 794 16

A large number of cell biological parameters are currently available to predict the prognosis of patients with breast cancer, but it is still difficulty accurately to predict the response to treatment. A valuable prognostic factor can be a poor predictive factor for response, and vice versa. High tumor levels of ER, PgR, AR and pS2 predict a relatively good response to endocrine therapy, while EGF-R positively, HER2/neu positivity, aneuploidy, high proliferation indices and possibly high uPA levels indicate a high chance of poor response to endocrine therapy in metastatic breast cancer. With respect to chemotherapy, a high proliferation rate and HER2/neu amplification predict a good response to therapy in metastatic disease, while MDR gene expression and possibly c-myc amplification are related to a worse response. In conclusion, the newer cell biological parameters can be used to select high and low-risk patients, type of systemic treatment, and as targets for new treatment modalities.
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PMID:Cell biological factors associated with the response of breast cancer to systemic treatment. 848 34


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