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)

Sentinel lymph node biopsy (SLNB) is being evaluated in breast cancer patients to improve detection of metastases and to guide therapy with minimal morbidity. The use of reverse transcription-PCR analysis to increase detection of tumor cells in SLN of breast cancer patients is hampered by the lack of specific markers. In this study, seven markers were evaluated by reverse transcription-PCR for expression in human breast adenocarcinoma lines (BrCa) and in normal nodes from non-cancer patients. Two markers yielded exceptional results; mammaglobin and carcinoembryonic antigen transcripts were detected in 100 and 71% BrCa, respectively, and were absent from all normal lymph nodes. These markers will be used as components of a multimarker panel to evaluate sentinel nodes in an on-going, multicenter clinical trial.
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PMID:Identification of superior markers for polymerase chain reaction detection of breast cancer metastases in sentinel lymph nodes. 978 5

The Mammaglobin gene, a breast-specific member of the uteroglobin gene family, has been previously identified as being overexpressed in some breast tumours, but the cellular origin and relationship to tumour progression are unknown. Using a subtractive hybridization approach, mammaglobin mRNA has also been found to be overexpressed in the in situ compared to the invasive element within an individual breast tumour. Further study by in situ hybridization performed in 13 breast tumours, selected to include normal, in situ, and invasive primary tumour elements, and in most cases axillary lymph node metastases, revealed that mammaglobin expression occurs in all elements, is restricted to epithelial cells, and is significantly increased in tumour cells compared with normal cells ( p< 0.04). Analysis of mammaglobin expression within 20 independent primary breast tumours and their corresponding axillary lymph nodes revealed that all 13 lymph nodes positive and none of the seven nodes negative for metastatic breast carcinoma by histology were mammaglobin-positive by reverse transcription-polymerase chain reaction (RT-PCR) ( p=0.0001). These results suggest that mammaglobin could be a marker of axillary lymph node breast metastases.
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PMID:Mammaglobin, a potential marker of breast cancer nodal metastasis. 1045 84

Sentinel lymph node (SLN) biopsy is being evaluated in breast cancer patients to improve detection of metastases and to guide therapy with minimal morbidity. The aim of this study was to increase the sensitivity of tumor cell detection in SLNs using superior reverse transcription polymerase chain reaction (RT-PCR) for carcinoembryonic antigen (CEA) and mammaglobin (MMG) analysis rather than current methods which fail to identify clinically relevant disease in many patients. In seventy stage I and II breast cancer patients dye-guided lymph node mapping was performed and the SLNs were divided alternately for RT-PCR or hematoxylin and eosin staining (H&E). RT-PCR and H&E diagnosis of SLNs were compared. SLNs were identified in 66/70 (94.3%) patients. Seventeen patients (26. 2%) had histological metastasis in SLNs. CEA was expressed in 25.0% of 48 patients with H&E negative SLNs, and MMG was expressed in 20. 8%. SLNs could predict axillary lymph node status with 95.4% accuracy and 6.3% false negative rate by H&E. Moreover, RT-PCR improved these to 98.5% and 2.8%, respectively. SLN diagnosis using RT-PCR is a powerful and sensitive method, which increases the accuracy of clinical staging and may provide more informed choices for appropriate therapeutic management of breast cancer patients.
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PMID:RT-PCR detection of breast cancer cells in sentinel lymph modes. 1081 88

The identification of specific tumor mRNA markers by reverse transcription-polymerase chain reaction might be a valuable diagnostic adjunct for the detection of breast cancer metastases in axillary sentinel lymph nodes (SLNs). In this study we have compared the diagnostic accuracy of an extensive histopathologic examination of 146 SLNs from 123 breast carcinoma patients with that of the evaluation of 5 mRNA markers. When analyzed individually, none of the different markers attained a sensitivity higher than 77.8%, and the general concordance with the histopathologic findings ranged from 78.8 to 83.6%. In a multiple-marker assay, taking into account the expression of at least 1 of the 5 tumor markers, the sensitivity of the test rose to 95.6%, with a specificity of 66.3% and a general concordance with the histopathologic status of 75.3%. Finally, when at least 2 of 3 markers (maspin, cytokeratin 19 and mammaglobin 1) were expressed, the concordance with either SLN or axillary lymph node status was highest (88.4% and 84.6%, respectively). The high prevalence of positive reverse transcription-polymerase chain reaction assays in histologically uninvolved SLNs, however, may hamper extensive application of these techniques in the clinical setting.
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PMID:Reverse transcription-polymerase chain reaction assay for multiple mRNA markers in the detection of breast cancer metastases in sentinel lymph nodes. 1149 30

Histological detection of axillary lymph node metastases is still the most valuable prognostic parameter for breast cancer, but about 30% of node-negative patients relapse within five years, suggesting that current methods are inadequate for identifying metastatic disease. More sensitive, PCR-based methods for the detection of metastatic cells are now available, enabling the amplification of cancer cell-specific mRNA messages by the RT-PCR assay. An ideal tumour marker, consistently expressed in tumour samples and not at all in normal lymph nodes, remains to be identified. The present study first investigated the expression of seven mRNA markers, CEA, CK19, c-Met, mammaglobin, MUC-1, beta1-->GalNAc-T and p97, selected on the basis of their previously reported specificity for breast cancer cells. Eighteen lymph nodes were examined from patients without tumours. Only mammaglobin mRNA and CEA mRNA were not expressed in normal nodes. All of the other markers showed a band of expression in 17%-55% of cases, indicating that they are not breast cancer-specific. CEA mRNA and mammaglobin mRNA expression could be detected in 15/20 (75%) and 19/20 (95%) primary breast carcinomas, respectively. The expression of mammaglobin mRNA and CEA mRNA was then compared in axillary lymph nodes from 248 consecutive breast cancer patients, 89 with histologically documented lymph node metastasis and 159 without histological evidence of metastatic disease. Ninety-seven per cent of the patients with histologically involved nodes showed expression of mammaglobin mRNA, whereas CEA mRNA was expressed in 79% of these cases. In the group of patients with histologically negative lymph nodes, 46 (29%) and 32 (20%) were found to be positive for mammaglobin and CEA expression, respectively, indicating the presence of metastases not detected by routine histological examination of one lymph node section. These results show that both mammaglobin RT-PCR and CEA RT-PCR are useful tools for the detection of breast cancer metastases in axillary lymph nodes. The detection sensitivity of the mammaglobin RT-PCR is far superior to that of the CEA RT-PCR, allowing the diagnosis of occult metastases in nearly one-third of cases.
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PMID:mRNA markers of breast cancer nodal metastases: comparison between mammaglobin and carcinoembryonic antigen in 248 patients. 1159 97

A stochastic model was developed to validate the results obtained with the mammaglobin-nested RT-PCR assay for tumor cell detection in peripheral blood of breast cancer patients. Since the assay consists of four PCR setups per peripheral blood sample, the probabilities for receiving 0, 1, 2, 3, or 4 positive setups were calculated. In this model, samples with just 500 mammaglobin mRNA molecules are highly probable to result in at least three positive setups, whereas lower quantities shift the probabilities towards one or two positive setups. In the clinical trial, samples with one or two mammaglobin positive setups were detected in 6/143 (4%) patients with benign lesions of the breast, in 41/310 (13%) breast cancer patients with no evidence of disease and in 39/157 (25%) breast cancer patients with metastatic disease. On the contrary, no sample from patients with benign lesions of the breast resulted in three or four positive setups, but 5/310 (2%) breast cancer patients with no evidence of disease and 46/157 (29%) with metastatic disease. These results correspond with the model: an increased number of tumor cells in peripheral blood lead to a higher amount of mammaglobin mRNA molecules, and these samples may result in at least three positive setups. Samples with three orfour positive setups were mainly derived from breast cancer patients with metastatic disease and only occasionally from patients with no evidence of disease. On account of these results, samples with at least three positive setups are of prognostic value and regarded as tumor cell positive.
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PMID:Statistical validation of the mammaglobin-nested RT-PCR assay for tumor cell detection in blood of breast cancer patients. 1176 65

To investigate the prognostic value of tumour cells in peripheral blood (pB) of breast cancer (BC) patients, pB samples from 143 patients with benign lesions of the breast and from 467 BC patients were tested via a nested RT-PCR assay for mammaglobin mRNA. No sample from patients with benign lesions of the breast was found to be mammaglobin positive in contrast to 5/310 (2%) BC patients with no evidence of disease (NED) and 46/157 (29%) patients with metastatic disease (MD). Two hundred and eighteen BC patients with NED were followed for at least 12 months. All five mammaglobin-positive BC patients relapsed 1-13 months after first examination of positive pB samples in contrast to 27/213 (13%) patients without detectable tumour cells in pB. Fifty-nine BC patients with MD were tested for mammaglobin expression in pB at the time of first diagnosis of MD; 20 of them (34%) were mammaglobin positive. Patients were followed for a median of 19 months (2-51 months). During this time, 19/59 (32%) died due to tumour progression. In Kaplan-Meier survival analysis, BC patients with mammaglobin-negative pB samples at time of diagnosis of MD lived significantly longer than mammaglobin-positive patients (log-rank test: P = 0.0013). In addition, mammaglobin was an independent prognostic parameter and the difference reached significance in univariate as well as in multivariate analysis (P < 0.01). We conclude that the presence of tumour cells in pB of BC patients is of prognostic value.
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PMID:Prognostic value of tumour cell detection in peripheral blood of breast cancer patients. 1250 58

Human mammaglobin (hMAM) mRNA is considered to be a promising candidate for a sensitive molecular marker for breast cancer. In this study, we attempted to relate the presence of hMAM mRNA in the peripheral blood with certain established clinicopathological features of breast cancer in order to validate its clinical utility. A total of 139 subjects including 79 with localized cancer, 33 with metastatic disease, and a control group of 27 individuals were studied. hMAM mRNA expression was assessed by reverse transcriptase polymerase chain reaction on cells from peripheral blood. The expression of hMAM mRNA was found in 0 of the 27 control subjects, 1 of the 8 stage 0 (12.5%) patients, 4 of the 16 stage I (25%) patients, 13 of the 40 stage II (32.5%) patients, 5 of the 15 stage III (33.3%) patients, and 18 of the 33 (54%) cases of metastatic disease. There was a statistically significant (P=0.045) difference in frequency between patients with localized disease (29%) and those with metastatic disease. Although trends of increasing frequency of hMAM mRNA expression existed in patients with unfavorable prognostic factors, including primary tumor size, T stage, N stage, overall stage, presence of angiolymphatic permeation, negative estrogen receptor, high 5-phase fraction (>7%), and aneuploid DNA index, none of the differences was significant. In conclusion, the clinical utility of hMAM mRNA may not be in screening or staging of breast cancer, but in following patients after surgery to detect recurrence. Further evaluation of hMAM mRNA in combination with other molecular markers to follow post-operative breast cancer patient is warranted.
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PMID:Lack of correlation between expression of human mammaglobin mRNA in peripheral blood and known prognostic factors for breast cancer patients. 1270 82

Ovarian cancer has the highest mortality rate of gynaecological cancers. This is partly due to the lack of effective screening markers. Here, we used oligonucleotide microarrays complementary to approximately 12 000 genes to establish a gene-expression microarray (GEM) profile for normal ovarian tissue, as compared to stage III ovarian serous adenocarcinoma and omental metastases from the same individuals. We found that the GEM profiles of the primary and secondary tumours from the same individuals were essentially alike, reflecting the fact that these tumours had already metastasised and acquired the metastatic phenotype. We have identified a novel biomarker, mammaglobin-2 (MGB2), which is highly expressed specific to ovarian cancer. MGB2, in combination with other putative markers identified here, could have the potential for screening.
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PMID:Predicting biomarkers for ovarian cancer using gene-expression microarrays. 1476 Mar 85

In the present study, we examined the expression of the mammaglobin genes, MGB1 and MGB2, in the sentinel lymph nodes (SLNs) of patients with breast cancer and compared our results with the histologic status of the same SLNs. Compared with immunohistochemical staining for cytokeratin 8, which detected metastases in 17 of 42 patients, reverse transcription-polymerase chain reaction (RT-PCR) for MGB1 or MGB2 genes was positive in 22 patients. The concordance between the expression of any mammaglobin and histologic status was 79% (33/42), with a sensitivity of 88% and specificity of 72%. The detection of patients with metastases was more sensitive when testing for both MGB1 and MGB2 (P < .0001) rather than MGB2 (P < .0005) or MGB1 (P < .05) alone. The increased detection rate relative to histologic examination suggests that using RT-PCR for the mammaglobin genes might identify patients at higher risk compared with patients with negative RT-PCR results.
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PMID:RT-PCR for mammaglobin genes, MGB1 and MGB2, identifies breast cancer micrometastases in sentinel lymph nodes. 1515 Dec 3


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