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)

Human epidermal growth factor receptor 2 (p185 HER2) oncoprotein immunohistochemical expression and DF3 antigen distribution were evaluated in 129 patients with primary breast cancer. p185 HER2 overexpession was positively correlated with the degree of differentiation, metastatic disease, progesterone receptors, and cytoplasmic distribution of DF3 antigen. p185 HER2 overexpression had prognostic significance for the disease-free interval.
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PMID:Immunohistochemical study of p185 HER2 and DF3 in primary breast cancer and correlation with CA-15-3 serum tumor marker. 1186 May 39

The study of different epithelial antigen expression has been performed in 183 breast cancers. In 73 patients regional lymph nodes were studied as well. Panepithelial antigen Egp-34 (Mab HEA-125) was expressed in 100% of primary tumors and metastases. Antigen MUC-1 (Mab ICO-25) was identified in 93% of breast cancers. Monomorphic type of expression in tumor cells was typical for Egp-34, MUC-1 being in certain cases expressed as a proportion of cells. Additional immunohistochemical study of regional lymph nodes with Mab to Egp34 and MUC-1 provides a 10% increase in the rate of breast cancer metastases detection compared to histological examination alone. The carcinoembryonic antigen (CEA) was useful in identification of metastases only in CEA-positive breast cancers.
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PMID:[The role of epithelial antigens in diagnosis and staging of breast cancer]. 1253 20

The sentinel node (SN) is the first lymph node in the lymphatic basin to be affected by metastasis from the primary tumour and is used to predict the status of the remaining nodes in the basin. We succeeded in detecting SNs of clinically early gastric cancers by intraoperative injection of a blue dye around the tumour. In the study presented here, multiple-marker reverse transcription-polymerase chain reaction (RT-PCR) was used to detect micrometastases in SNs and results were compared with those obtained with conventional histology. Expressions of cytokeratin-18 (CK-18), carcinoembryonic antigen (CEA), human telomerase reverse transcriptase (hTRT) and MUC-1 in SNs were determined by RT-PCR and Southern blot assay. Of the 213 SNs obtained from 35 cases of gastric cancer, eight nodes (3.8%) from five patients contained metastases that could be identified by conventional histology. However, CK-18 mRNA was expressed in 15 (7.0%), CEA in 12 (5.6%), hTRT in 10 (4.7%), and MUC-1 in 12 (5.6%) nodes, with at least one mRNA marker expressed in 25 nodes (11.7%) obtained from six patients. In the five patients with nodal metastases identified by conventional histology, two had metastases in both SNs and non-SNs. And, in the 30 patients without nodal metastases identified by conventional histology, one patient with micrometastases in the SNs identified by RT - PCR and Southern blot assay also had metastases in non-SNs as identified by serial sectioning and immunostaining of CK-18. All additional metastases were detected in non-SNs located in the same lymphatic basin as the previously detected SNs. This suggests that lymph node dissection of early-stage gastric cancer in the lymphatic basin may be mandatory even for patients without histologically detectable metastases in SNs.
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PMID:Micrometastases in sentinel nodes of gastric cancer. 1291 77

The object of this study was to examine whether MUC-1 can be detected in the axillary lymphatic drainage of patients who have undergone conservative surgery for breast cancer and to assess the correlations between the presence of MUC-1 and prognostic factors in breast cancer. Sixty-eight women with invasive ductal carcinoma of the breast underwent wide local excision and axillary lymph node dissection. Axillary drains were inserted in all these cases, and the presence of MUC-1 and beta-actin was evaluated by RT-PCR in the lymphatic fluid collected after the operation. Prognostic factors included tumour size and grade, vascular and lymphatic invasion, clearance margins of the resected specimens and status of the axillary lymph nodes. RT-PCR assays for MUC-1 in the axillary fluid were positive in 17 patients (25%). The presence of MUC-1 was associated with increased tumour size and showed a positive correlation with axillary lymph node metastases and incomplete resection of the tumour. RT-PCR can disclose cancer cells in the axillary fluid after conservative surgery for breast cancer. The presence of MUC-1 in the axillary drainage may be associated with poor prognostic features, and its detection may have implications for therapy as it suggests that re-excision should be considered.
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PMID:Detection of cancer cells in the axillary drainage using RT-PCR after operations for breast cancer. 1475 16

We examined axillary lymph nodes from 26 patients with node-negative breast cancer managed by axillary node sampling and no further axillary treatment, but who subsequently developed axillary recurrence after a mean follow-up of 7 years to determine the incidence of micrometastatic disease in these patients. Twenty-six matched controls with an identical length of follow-up who were node-negative on an axillary node sample, but have not developed axillary recurrence, also underwent node examination and the incidence of metastases in the two groups were compared. Lymph nodes were sectioned at two additional levels 100 microm apart. Sections at each level were stained with haematoxylin and eosin (H&E) and antibodies to PanCK and MUC1 protein. The original H&E section from each node was reviewed and additional sections from each lymph node were examined by a pathologist who was blinded to outcome. Review of the original H&E sections of the nodes revealed metastases that had been overlooked at the time of diagnosis in two (8%) patients from the recurrence group. A further two (8%) patients from the recurrence group and three (12%) from the control group had axillary nodes which contained micrometastases. Immunocytochemistry was important in identifying all micrometastases. There was no significant difference in the incidence of axillary node micrometastases between patients with and without axillary node recurrence. Although the number of cases was small, this study suggests that axillary recurrence following a negative sampling procedure is not commonly due to missed axillary node metastases.
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PMID:Occult lymph node metastases in patients with 'node negative' breast carcinoma treated with conservation surgery and axillary node sample and who subsequently developed axillary recurrence. 1496 75

Androgen withdrawal is the only effective therapy for patients with advanced prostate cancer, but progression to androgen independence ultimately occurs in almost all patients. Novel therapeutic strategies targeting molecular mechanisms that mediate resistance to hormonal and chemotherapeutic treatment are highly warranted. Here, we aimed to evaluate the expression of potential therapeutic targets in advanced prostate cancer. A tissue microarray (TMA) containing samples from 535 tissue blocks was constructed, including benign prostatic hyperplasia as controls (n = 65), prostatic intraepithelial neoplasia (PIN; n = 78), clinically localized prostate cancers (n = 181), as well as hormone-refractory local recurrences (n = 120) and distant metastases (n = 91). The expression of 13 different proteins was analyzed using immunohistochemistry (Bcl-2, p53, ILK, Syndecan-1, MUC-1, EGFR, HER2/neu, HSP-90, Ep-CAM, MMP-2, CD-10, CD-117 and Ki67). Significant overexpression in hormone-refractory prostate cancer and metastatic tissue compared to localized prostate cancer was found for Ki67 (64% vs. 9%), Bcl-2 (11% vs. 1%), p53 (35% vs. 4%), Syndecan-1 (38% vs. 3%), EGFR (16% vs. 1%) and HER2/neu (16% vs. 0%). Overexpression of CD-117 was restricted to 1 single metastasis. All other markers did not show relevant differences in expression between subgroups. Taken together, p53, Bcl-2, Syndecan-1, EGFR and HER2/neu are preferentially expressed in hormone-refractory and metastatic prostate cancer. Selected inhibition of these targets might offer a strategy to treat advanced tumors and prevent further progression. Treatment decisions should not be based on findings in primary tumors but rather on tissues from recurrent or metastatic lesions.
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PMID:Expression patterns of potential therapeutic targets in prostate cancer. 1547 3

Pancreatobiliary and ampulla of Vater adenocarcinomas frequently metastasize to regional lymph nodes, liver, or lung and are difficult to diagnose because they lack specific immunohistochemical markers. We studied the expression of cytokeratin 7 (CK7), cytokeratin 17 (CK17), cytokeratin 20 (CK20), CDX2, mucin 1 (MUC1), mucin 2 (MUC2), and mucin 5AC (MUC5AC) in 46 cases of pancreatic ductal carcinoma, 18 ampulla of Vater adenocarcinomas, and 24 intrahepatic cholangiocarcinomas. The expression of MUC1 and CK17 was restricted to pancreatic ductal carcinoma (41 of 46, 89%; 38 of 46, 83%, respectively), the ampullary carcinoma of pancreatobiliary origin (6 of 6, 100%; 5 of 6, 83%, respectively), and intrahepatic cholangiocarcinoma (20 of 24, 83%; 17 of 24, 71%, respectively). More than 50% of cases of pancreatobiliary adenocarcinomas showed diffuse cytoplasmic CK17 positivity. In contrast, less than 5% cases (8 of 184) of extra-pancreatobiliary nonmucinous adenocarcinomas expressed CK17, and only 3 of them showed diffuse CK17 positivity. The expression of MUC2 and CDX2 was restricted to the intestinal, mucinous, and signet-ring cell-type adenocarcinomas of duodenal papillary origin (9 of 11, 82%; 11 of 11, 100%, respectively). MUC2 was rarely expressed in pancreatic ductal carcinoma (1 of 46, 2%) and was negative in the ampullary carcinoma of pancreatobiliary origin and in intrahepatic cholangiocarcinoma. A heterogeneous CDX2 staining pattern was seen in 1 of 6 cases of the ampullary carcinoma of pancreatobiliary origin (17%), 5 of 24 intrahepatic cholangiocarcinomas (21%), and 10 of 46 (22%) pancreatic ductal carcinomas. In contrast, all 11 cases of the intestinal, mucinous, and signet-ring cell-type adenocarcinomas of duodenal papillary origin showed homogeneous CDX2 nuclear positivity. We concluded that CK17 is a useful marker in separating pancreatobiliary adenocarcinomas from extra-pancreatobiliary nonmucinous adenocarcinomas, including adenocarcinomas from the colon, breast, gynecologic organs, stomach, lung, prostate, thyroid, kidney, and adrenal gland, and malignant mesothelioma. MUC1+/CK17+ can be used as positive markers for pancreatic ductal carcinomas, the ampullary carcinoma of pancreatobiliary origin, and cholangiocarcinomas with positive predictive values of 76%, 83%, and 58%, respectively. MUC2+/CDX2+ can be used as positive markers for the intestinal-type adenocarcinoma of duodenal papillary origin with a positive predictive value of 82%.
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PMID:Immunohistochemical staining in the diagnosis of pancreatobiliary and ampulla of Vater adenocarcinoma: application of CDX2, CK17, MUC1, and MUC2. 1572 5

MUC1 (mucin 1) is a transmembrane glycoprotein normally expressed on epithelia of the pancreas, breast, prostate, colon, and lung. However, this self-antigen is over-expressed and aberrantly glycosylated in adenocarcinomas, thereby making it a potential target for immunotherapy. Toward this goal, DNA plasmids encoding human MUC1 (pMUC1) and mouse interleukin-18 (pmuIL-18) were developed, and previous work demonstrated pMUC1/pmuIL18 vaccination protected MUC1 transgenic mice (MUC1.Tg) from subcutaneous tumor challenge. This report shows that pMUC1/pmuIL-18 is effective in preventing and treating pulmonary metastases in MUC1.Tg mice. Vaccination with pMUC1 or pmuIL-18 alone was insufficient to elicit measurable anti-tumor effects. However, co-administration of pMUC1 with pmuIL-18 reduced the incidence of lung tumors and prolonged survival. Furthermore, pMUC1/pmuIL-18 immunization protected mice from challenge with MUC1+ tumors, but not from MUC1- tumors, indicating that the anti-tumor effect is antigen-specific. More importantly, pMUC1/pmuIL-18 was effective in treating established tumors. Finally, in vivo antibody-mediated lymphocyte depletion and neutralization of interferon gamma (IFNgamma) revealed that CD8+ T cells and IFNgamma mediate the anti-tumor immunity. Collectively, these results demonstrate that pMUC1/pmuIL-18 breaks tolerance to MUC1, and induces antigen-specific immunity with protective and therapeutic benefit. This suggests that pMUC1/pmuIL-18 DNA vaccination may provide clinical benefit for patients with MUC1+ tumors.
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PMID:Intradermal vaccination of MUC1 transgenic mice with MUC1/IL-18 plasmid DNA suppresses experimental pulmonary metastases. 1729 19

Aptamers are functional molecules able to bind tightly and selectively to disease markers, offering great potential for applications in disease diagnosis and therapy. MUC1 is a well-known tumour marker present in epithelial malignancies and is used in immunotherapeutic and diagnostic approaches. We report the selection of DNA aptamers that bind with high affinity and selectivity an MUC1 recombinant protein containing five repeats of the variable tandem repeat region. Aptamers were selected using the SELEX methodology from an initial library containing a 25-base-long variable region for their ability to bind to the unglycosylated form of the MUC1 protein. After ten rounds of in vitro selection and amplification, more than 90% of the pool of sequences consisted of target-binding molecules, which were cloned, sequenced and found to share no sequence consensus. The binding properties of these aptamers were quantified using ELISA and surface plasmon resonance. The lead aptamer sequence was subsequently used in the design of an aptamer-antibody hybrid sandwich ELISA for the identification and quantification of MUC1 in buffered solutions. Following optimisation of the operating conditions, the resulting enzyme immunoassay displayed an EC50 value of 25 microg/ml, a detection limit of 1 microg/ml and a linear range between 8 and 100 microg/ml for the MUC1 five tandem repeat analyte. In addition, recovery studies performed in buffer conditions resulted in averaged recoveries between 98.2 and 101.7% for all spiked samples, demonstrating the usability of the aptamer as a receptor in microtitre-based assays. Our results aim towards the formation of new diagnostic assays against this tumour marker for the early diagnosis of primary or metastatic disease in breast, bladder and other epithelial tumours.
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PMID:DNA aptamers against the MUC1 tumour marker: design of aptamer-antibody sandwich ELISA for the early diagnosis of epithelial tumours. 1769 98

MUC1 (CD227), an established tumor marker, is expressed on glandular epithelia and on epithelial tumors. Tumor MUC1 differs from normal MUC1 by modified glycan side chains. Recently, a novel carbohydrate-induced conformational tumor-associated MUC1 epitope (TA-MUC1) was described, whose clinical relevance in lung cancer is not known. Eighty-five paraffin embedded tissue sections of non-small cell lung cancer (NSCLC) patients (73% male; mean age 64+/-9 years) were stained with the monoclonal antibody PankoMab (against TA-MUC1) and compared with the established antibodies E29 and 214D4 regarding prognostic relevance. TA-MUC1 is virtually absent in bronchial epithelium. As shown by multivariate analysis, only staining with PankoMab, but not with E29 or 214D4, was correlated with patients' survival (p=0.029). Moreover, when regarding interactions of MUC1 antibody staining results and clinico-pathological parameters, patients with lymph node metastasis lacking PankoMab staining were attributed the highest risk by far (Hazard ratio=4.6, 95% CI: 2.1-9.7, p=0.000). In summary, the presence of TA-MUC1 is a favorable prognostic factor in this cohort of NSCLC patients, in particular if lymph node metastases are present. This is in contrast to the results for E29 and 214D4, which recognize less or not glycosylation dependent epitopes. As this is the first report on a well-defined MUC1 epitope associated with improved survival in NSCLC, a more differentiated view on MUC1 may be mandatory.
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PMID:TA-MUC1 epitope in non-small cell lung cancer. 1853 57


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