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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Perturbations of oncogenes in breast carcinoma include amplifications of the HER-2/neu and PRAD1 genes, as well as p53 mutations. Some of these lesions frequently appear in early cancers such as ductal carcinoma in situ and are stable as the tumors become invasive and metastasize. Thus these findings suggest that oncogene mutations may define a point of origin for a given breast cancer, and are fixed lesions during tumor progression. Such germline abnormalities may occur at the BRCA1, H-RAS VNTR, and p53 loci. The rational use of genetics may be to identify women at high risk for the development of breast cancer so that they may be enrolled in future chemoprevention trials.
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PMID:Oncogenes, breast cancer, and chemoprevention. 800 94

The recent advances in the understanding of the pathogenesis of ovarian cancer have been helpful in addressing issues in diagnosis, prognosis and management. The study of ovarian tumours by novel techniques such as immunohistochemistry, fluorescent in situ hybridisation, comparative genomic hybridisation, polymerase chain reaction and new tumour markers have aided the evaluation and application of new concepts into clinical practice. The correlation of novel surrogate tumour specific features with response to treatment and outcome in patients has defined prognostic factors which may allow the future design of tailored therapy based on a molecular profile of the tumour. These have also been used to design new approaches to therapy such as antibody targeting and gene therapy. The delineation of roles of c-erbB2, c-fms and other novel receptor kinases in the pathogenesis of ovarian cancer has led initially to the development of anti-c-erbB2 monoclonal antibody therapy. The discovery of BRCA1 and BRCA2 genes will have an impact in the diagnosis and the prevention of familial ovarian cancer. The important role played by recessive genes such as p53 in cancer has raised the possibility of restoration of gene function by gene therapy. Although the pathological diagnosis of ovarian cancer is still confirmed principally on morphological features, addition of newer investigations will increasingly be useful in addressing difficult diagnostic problems. The increasingly rapid pace of discovery of genes important in disease, makes it imperative that the evaluation of their contribution in the pathogenesis of ovarian cancer is undertaken swiftly, thus improving the overall management of patients and their outcome.
Cancer Metastasis Rev 1997 Jun
PMID:Molecular approaches to diagnosis and management of ovarian cancer. 915 81

Sporadic breast carcinoma is associated with multiple genetic alterations. The clinical relevance of these alterations, however, needs further clarification. In the present study we analyzed 266 spontaneously arising breast carcinomas for allelic losses in the BRCA1 and TP53 regions on chromosome 17, the BRCA2 region on chromosome 13, the ATM (mutated in ataxia-telangiectasia) region on chromosome 11 and on the chromosomal arms 7q and 16q. In addition the following clinical and pathological parameters were evaluated: age at diagnosis, tumor size, presence or absence of regional and distant metastases, hormone-receptor status, histopathological classification and tumor grading. The analysis of genetic and clinical observations revealed significant associations: absence of expression of the estrogen receptor was linked to a high rate of allelic losses of markers in the BRCA1, TP53 and BRCA2 regions. Expression of the progesterone receptor coincided with allelic loss on the long arm of chromosome 16. High-grade malignant lesions and ductal differentiation were frequently associated with allelic losses in the proximal portion of chromosome 17q. The accumulation of multiple allelic deletions was linked to high-grade malignant tumors, to tumor size, and to loss of expression of the estrogen receptor. Our data point to a relationship between clinically relevant prognostic factors and specific genomic deletions in the BRCA1, BRCA2 and TP53 region.
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PMID:Genomic deletions in the BRCA1, BRCA2 and TP53 regions associate with low expression of the estrogen receptor in sporadic breast carcinoma. 922 12

Factors affecting the penetrance and expression of BRCA1 are not understood. Breast cancer risk and ovarian cancer risk, in general, are known to be associated with non-Mendelian factors. However, whether and how these various factors influence tumor development in BRCA1 mutation carriers is not known. Here we report the breast and ovarian cancer syndrome in an identical twin pair. These female identical twins had remarkably similar clinical histories. Both twins developed histologically similar ovarian cancer in their mid-fifties. One twin was diagnosed with stage III disease and died of refractory metastatic disease. The other twin was diagnosed with stage I disease but ultimately died of recurrent disease. Neither twin developed breast or colon cancer. The twins have both similarities and differences in terms of nongenetic cancer-related risk factors. Results of BRCA1 analysis of DNA from both twins revealed a novel mutation, 2711delA, which resulted in a premature termination at codon 892. This report has intriguing implications concerning the role of genotype in the ultimate penetrance and expression of disease among BRCA1 mutation carriers.
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PMID:A novel BRCA1 mutation in an identical twin pair with similar clinical histories. 940 79

Gene diagnosis has been mainly performed for three purposes, 1) to assess the prophylactic risk from genetic alterations of candidate gene, 2) to confirm the diagnosis from a small volume of cancer cells using polymerase chain reaction method and 3) to understand the biological characteristic of the tumor by assessing genetic instabilities. BRCA1 and BRCA2 are quite important candidate genes in familial breast cancer. Recently, prophylactic mastectomy has been performed for BRCA1/2 carriers in Western countries. Telomerase activity can be a sensitive and definitive analysis for diagnosing certain cancers, and the reverse transcripted polymerase chain reaction (RT-PCR) method can detect a small number of metastatic cancer cells in the axillary lymph node. Furthermore, genetic abnormalities, such as abnormalities in oncogenes or/and tumor suppressor genes and loss of heterozygosity or microsatellite instability, facilitate understanding of the biological characteristics of these tumors. It is necessary for the clinician to understand the significance and usefulness of gene diagnosis.
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PMID:[Clinical value of gene diagnosis in breast cancer]. 980 Apr 71

To improve the diagnosis and treatment of cancer, an increased understanding of the molecular and cellular changes that regulate metastatic ability is required. We have recently demonstrated a prostate cancer metastasis-suppressor activity encoded by a discontinuous approximately 70-cM region of human chromosome. The presence of this region suppresses the spontaneous metastatic ability of AT6.1 rat prostatic cancer cells by greater than 30-fold (M. A. Chekmareva et al., Prostate, 33: 271-280, 1997). Interestingly, a number of potentially important genes which have been mapped to human chromosome 17, including TP53, NM23, and BRCA1, are not retained (M. A. Chekmareva et al., cited above) or are not expressed in these microcell hybrids (B. A. Yoshida et al., In Vivo, in press), which suggests the presence of a novel metastasis-suppressor gene(s) or novel function of a known gene(s) encoded by this region(s). We hypothesize that identification of the "step" in the metastatic cascade that is inhibited by the presence of the approximately 70-cM metastasis-suppressor region will facilitate the identification of candidate metastasis-suppressor genes. For a cancer cell to metastasize, it must escape from the primary tumor, enter the circulation, arrest in the microcirculation, extravasate into a tissue compartment, and grow. This suppression of spontaneous macroscopic lung metastases could be due to the inhibition of a number of steps within this cascade. Results of the current study demonstrate that AT6.1 cells containing the approximately 70-cM region (AT6.1-17-4 cells) escape from the primary tumor and arrest in the lung but are growth-inhibited unless the metastasis-suppressor region is lost. This growth inhibition seems to result from an effect of one or more genes at the metastatic site and not from a circulating angiogenesis inhibitor. Our findings suggest that the approximately 70-cM region of human chromosome 17 may encode a gene(s) that regulates the "dormancy" of AT6.1-17-4 micrometastases.
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PMID:Chromosome 17-mediated dormancy of AT6.1 prostate cancer micrometastases. 981 6

The goal of our study was to develop a panel of tumor cell lines along with paired non-malignant cell lines or strains collected from breast cancers, predominantly primary tumors. From a total of 189 breast tumor samples consisting of 177 primary tumors and 12 metastatic tissues, we established 21 human breast tumor cell lines that included 18 cell lines derived from primary tumors and 3 derived from metastatic lesions. Cell lines included those from patients with germline BRCA1 and FHIT gene mutations and others with possible genetic predisposition. For 19 tumor cell lines, we also established one or more corresponding non-malignant cell strains or B lymphoblastoid (BL) lines, which included 16 BL lines and 7 breast epithelial (2) or stromal (5) cell strains. The present report describes clinical, pathological and molecular information regarding the normal and tumor tissue sources along with relevant personal information and familial medical history. Analysis of the breast tumor cell lines indicated that most of the cell lines had the following features: they were derived from large tumors with or without axillary node metastases; were aneuploid and exhibited a moderate to poorly differentiated phenotype; were estrogen receptor (ER)- and progesterone receptor (PR)-negative; and overexpressed p53 and HER2/neu proteins. Of 13 patients with primary breast cancers receiving curative intent mastectomies, 7 were dead after a mean period of 10 months. Our panel of paired tumor and non-malignant cell lines should provide important new reagents for breast cancer research.
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PMID:Characterization of paired tumor and non-tumor cell lines established from patients with breast cancer. 983 71

Genetic alterations of tumour suppressor genes, for which loss of heterozygosity (LOH) is one mechanism of gene inactivation, are important steps in the development of endometrial cancer. To investigate the clinical relevance of LOH of BRCA1 (17q21), TP53 (17p13) and TCRD (14q11) in endometrial cancer, polymerase chain reaction (PCR)-based fluorescent DNA technology for the detection of microsatellite polymorphisms was applied. One hundred and thirteen archival endometrial cancer samples with matched normal tissues were examined. Allele loss at three loci were correlated with age, tumour size, lymph node status, metastases, stage, histological types, grade, expression of oestrogen receptor (ER) and progesterone receptor (PgR), family history of cancer, previous history of cancer or precursor lesions, and previous history of hormone replacement therapy (HRT). LOH for BRCA1 was detected in 18.1%, of TP53 in 26.9%, and of TCRD in 26.3% of informative cases. LOH of BRCA1 correlated with medium grade, positive ER status, and family history of cancer; LOH of TP53 correlated with younger age, high grade, positive PgR status, and with tumours from patients without HRT; LOH of TCRD correlated only with family history of cancer. LOH at all three loci correlated only with grade and positive family history. Allele loss of one of the three tumour suppressor loci did not correlate with disease-free survival (DFS), but LOH of BRCA1 correlated significantly with decreased overall survival (OS). The latter, together with the correlation of LOH of BRCA1 locus with steroid hormone receptor expression, might give a hint to the potential involvement of the co-localised 17 beta-hydroxysteroid dehydrogenase (HSD) gene in the development of endometrial cancer.
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PMID:Loss of heterozygosity of BRCA1, TP53 and TCRD markers analysed in sporadic endometrial cancer. 989 67

We know that breast cancer is already a systemic disease in the majority of patients at the time it is first diagnosed, requiring an interdisciplinary treatment concept. This fact has changed the surgical treatment approach of primary breast cancer which currently follows the principle: "As much as necessary, as little as possible". Improved early detection of breast carcinomas allows the treatment of a majority of early stage breast cancer patients with breast-conservation surgery, followed by irradiation except for a few contraindications. Although survival is not significantly different for patients who undergo breast conservation surgery plus irradiation than for those having modified radical mastectomy, the pattern and prognostic value of locoregional failure are different. Locoregional failure after breast conservation requires mastectomy, thoracic wall recurrence will be treated by (en-bloc) resection and irradiation. Following rigorous selection criteria and indications, surgical resection of distant metastases to the liver, lung or brain can improve the quality of life and prolong survival, it should therefore be taken into consideration in individual cases. Since the two breast cancer susceptibility genes, BRCA1 and BRCA2, have been detected, high-risk patients should be offered the possibility of genetic counseling and genetic testing. Based on our present knowledge, the surgical approaches for BRCA1 or BRCA2 mutation carriers with breast cancer remain unchanged. There are some indications that molecular tumor parameters can be used to identify a subgroup of primary breast cancer patients who are characterized by a poorer prognosis. The results achieved in our own patients add further evidence in favor of this theory.
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PMID:[Surgical procedure in primary and metastatic breast carcinoma]. 1006 81

Loss of heterozygosity (LOH) in loci of the 17q21 and 13q12-13 regions can collaborate in the inactivation of BRCA1, BRCA2, and possibly other genes implicated in the pathogenesis of breast carcinomas. We investigate allelic losses in microsatellites of the BRCA1 and BRCA2 regions, and their correlations with seven pathologic parameters in 140 breast carcinomas. Those cases showing LOH in the region of the RB gene, 13q14, were excluded from the study. The LOH analysis was performed by amplifying DNA by PCR, using four markers of the 17q21 region (D17S856, D17S855, D17S1323, and D17S1327) and four markers of the 13q12-13 region (D13S290, D13S260, D13S310, and D13S267). LOH in the BRCA1 region was found in 47% of tumors, correlating significantly with estrogen receptor content (p = 0.025), progesterone receptors (p = 0.004), higher grade (p = 0.0008), peritumoral vessel invasion (p = 0.001), and lymph node metastases (p = 0.002). When we excluded the cases with LOH in the BRCA2 region and those not informative for it, the significance disappeared. In the BRCA2 region, a rate of LOH of 51% was found; it correlated significantly with estrogen receptor content (p = 0.002), progesterone receptors (p = 0.03), peritumoral vessel invasion (p = 0.005), higher grade (p = 0.002), and lymph node metastases (p = 0.001). When cases with BRCA1 losses and those not informative were excluded, again the significance disappeared. Concomitant losses in the BRCA1 and BRCA2 regions were found in 32% of cases, correlating significantly with lymph node metastases (p = 0.0002), estrogen receptor content (p = 0.003), progesterone receptors (p = 0.001), histologic grade (p = 0.01), and peritumoral vessel invasion (p = 0.0004). These results suggest that concomitant losses in both regions could have a functional effect, influencing the presence of a poor tumor pathophenotype in breast carcinomas.
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PMID:Loss of heterozygosity in BRCA1 and BRCA2 markers and high-grade malignancy in breast cancer. 1020 68


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