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)

Expression of bcl-2 is most commonly associated with the t(14;18) translocation present in most folicular lymphomas (1). More recently, bcl-2 oncoprotein has been identified in normal tissues and in nonhematologic malignancies. In this study, we investigate the use of bcl-2 as a marker to distinguish metastatic breast carcinoma from primary lung and gastric cancers, and we evaluate the role of bcl-2 as an independent prognostic factor in breast carcinoma and its relationship to other breast cancer markers. bcl-2 immunostains were done on 371 adenocarcinomas of the breast, lung, and stomach. Additionally, 231 samples of metastases from patients with breast or gastric cancer were evaluated for bcl-2 expression. All breast cancer tissue samples had immunohistochemical data on expression of estrogen and progesterone receptors, p53, neu/cerb2, and MIB-1. A large proportion (79.3%) of invasive breast carcinomas expressed bcl-2, whereas only 5.6% and 8.3% of pulmonary and gastric carcinomas did. Moreover, staining was moderate to intense in 70.2% of the breast cancers, compared with only one specimen of lung carcinoma (1.9%) and gastric carcinoma (0.9%) that showed moderate staining. There was agreement of bcl-2 expression between primary and metastatic sites in all specimens except one. Expression of bcl-2 in breast adenocarcinomas was significantly associated with hormone receptor positivity and low histologic grade. Nonetheless, 20.6% of bcl-2-positive specimens were estrogen receptor negative and 24.2% of bcl-2-positive specimens were progesterone receptor negative. Neither the presence nor the absence of bcl-2 expression significantly predicted disease-free survival or overall survival in patients with breast cancer. We conclude that adenocarcinomas with intense bcl-2 staining are more likely to be of breast than of pulmonary or gastric origin. We recommend the addition of bcl-2 to a panel of antibodies (estrogen receptor, GCDFP-15, and S100) that might contribute to the identification of a larger proportion of metastatic breast carcinomas, because almost one-half of the estrogen-receptor negative cancers were bcl-2 positive.
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PMID:Expression of bcl-2 by breast cancer: a possible diagnostic application. 872 86

Immunohistochemical expression of p53, bcl-2, CD44 standard (CD44S), and the v6 isoform of CD44 (CD44v6) proteins were studied in 14 typical carcinoid tumors (TCs), 11 atypical carcinoids (ACs), and eight small cell carcinomas (SCLCs) in an attempt to use these markers of mutational events and cellular adhesion to discriminate neoplasms demonstrating neuroendocrine differentiation. p53 and bcl-2 overexpression were associated with more aggressive neuroendocrine cell types. p53 nuclear staining was weakly positive in 21% of the TCs, whereas strong nuclear staining was seen in 64% of the ACs and 88% of the SCLCs (P = 0.0047). bcl-2 was present in 21% of the TCs, 91% of the ACs, and 100% of the SCLCs (P = 0.0001). In contrast, CD44S and CD44v6 were inversely correlated with more aggressive types of neuroendocrine tumors. CD44S expression was moderate to strong in all of the TCs and 91% of the ACs but in only 37% of the SCLCs (P = 0.0018). There was no correlation between expression of these markers and tumor size or nodal status, although loss of CD44v6 was associated with lymph node metastases in the TC group only. In the spectrum of neuroendocrine tumors of the lung, p53 and bcl-2 overexpression correlates with more aggressive histologic cell types. The decreasing CD44S expression in AC and SCLC is similar to findings in cancer of the colon and in non-small cell carcinoma of the lung, where loss of CD44S is associated with poor prognosis. In AC and SCLC, but not in cancer of the colon, loss of CD44v6 correlates with more aggressive neoplasms and might correlate with lymph node metastases in TCs.
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PMID:Bcl-2, p53, CD44, and CD44v6 isoform expression in neuroendocrine tumors of the lung. 873 62

Twenty cases of ovarian carcinoma with normal-sized ovaries were examined histologically. Fifteen of them had metastatic disease of the peritoneal cavity and three of the remaining showed uterine involvement. Only in one case was the tumor confined to the ovary, but this patient had experienced systemic chemotherapy before surgery. The remaining case had metastasis of the stomach. Thus, "normal-sized" ovarian carcinoma has a great tendency to spread externally. Histology of the carcinoma was that of common epithelial carcinoma of the ovary with variable degrees of differentiation except for three cases of apparent ovarian metastasis. No cases of definite mesothelioma with ovarian involvement were encountered. A search for determinants of the peritoneal spread was performed using immunohistochemistry for p53 and bcl-2 proteins. However, no differences were found in the antigen expression between the group with and without peritoneal metastasis.
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PMID:Pathological aspects of normal-sized ovarian carcinoma. 875 May 10

Programmed cell death (apoptosis) is now recognized as an important factor in tumour growth. Bcl-2 is an oncogene which promotes tumour progression by specifically inhibiting programmed cell death. Bcl-2 oncoprotein was measured using flow cytometry in 42 surgically excised regional lymph node metastases from patients with a median follow-up of 45 months. Fifteen patients in the study were found to have bcl-2 expression which was associated with significantly shorter survival (log-rank test, P<0.002). In addition, multivariate analysis confirmed the predictive value of bcl-2 independent of other established prognostic markers (chi(2)=7.02, P<0.01). Oncogenic control of programmed cell death is therefore important in melanoma progression and bcl-2 measurement provides a useful marker of prognosis for regional lymph node metastases.
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PMID:Bcl-2 expression in malignant melanoma and its prognostic significance. 878 49

In order to clarify the factors that affect growth of endometrial carcinoma, immunohistochemical analyses of bcl-2, p53, sex steroid receptors, and Ki-67 were performed in 35 cases of endometrial carcinoma (32 endometrioid and three clear-cell carcinomas). Correlation of antigen expression with clinicopathological features was analyzed. Expression of bcl-2 was found in 58.8, 33.3, and 20.0% of grade 1 (G1), grade 2 (G2), and grade 3 (G3) endometrial carcinomas, respectively. Estrogen receptor (ER) was observed in 70.6, 22.2, and 0% of G1, G2, and G3 cases (p < 0.01), respectively. In contrast, expression of p53 was found in 5.8, 33.3, and 60.0% of G1, G2, and G3 cases, respectively. The labeling index of Ki-67 correlated with p53 overexpression (p < 0.01). Lymph node metastases were observed in 6.6 and 5.5% of ER- and PR (progesterone receptor)-positive carcinomas, whereas metastases were observed in 44.4 and 53.3% of ER- and PR-negative carcinomas, respectively (p < 0.05). Lymph node metastases were observed in 50.0% of p53-positive carcinomas, whereas metastases were observed in 22.2% of p53-negative carcinomas (p < 0.05). These results suggest that bcl-2 expression in endometrial carcinomas is regulated in a hormone-dependent manner. Expression of bcl-2 may occur more frequently in estrogen-related, low-grade endometrial carcinomas, whereas p53 overexpression is found more often in endometrial carcinomas in estrogen-unrelated, high-grade endometrial carcinomas with prominent proliferative activity and a high frequency of lymph node metastases.
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PMID:Immunohistochemical analysis of endometrial adenocarcinoma for bcl-2 and p53 in relation to expression of sex steroid receptor and proliferative activity. 881 80

The erbB-2 receptor plays an important role in the prognosis of breast cancer and is expressed at high levels in nearly 30% of tumors in breast cancer patients. While evidence accumulates to support the relationship between erbB-2 overexpression and poor overall survival in human breast cancer, understanding of the biological consequence(s) of erbB-2 overexpression remains elusive. The discovery of heregulin has allowed us to identify a number of related but distinct biological endpoints which appear responsive to signal transduction through the erbB-2/4 receptor. These endpoints of growth, invasiveness, and differentiation have clear implications for the emergence, maintenance, and/or control of malignancy, and represent established endpoints in the assessment of malignant progression in human breast cancer. Preliminary studies in vitro have shown that heregulin induces a biphasic growth effect on cells with erbB-2 overexpression. Interestingly, we observed that expression of heregulin correlates with a more aggressive/invasive, vimentin-positive phenotype in breast cancer cells lines. Therefore, we have postulated that heregulin is involved in breast cancer tumor progression. We have shown that heregulin induces in vitro chemoinvasion and chemotaxis of breast cancer cells as well as growth in an anchorage dependent and independent manner. Interestingly, a heregulin neutralizing antibody inhibits chemotaxis and results in cell growth inhibition and blockade of the invasive phenotype. Strikingly, genetically engineered cells which constitutively express heregulin demonstrate critical phenotypic changes that are associated with a more aggressive phenotype. Specifically, these cells are no longer dependent on estrogen for growth and are resistant to tamoxifen in vitro and in vivo, and moreover these cells metastasize to lymph nodes in athymic nude mice. These tumors appear to have lost bcl-2 expression as compared with the control tumors. In addition, presumably by activation/regulation of topoisomerase II, the heregulin-transfected cells become exquisitely sensitive to doxorubicin and VP-16. Clearly, mechanistic aspects of the erbB-2/4 and heregulin interaction need to be understood from a therapeutic standpoint which could provide additional insights into synergistic treatments for certain patients, or improve treatment regimens for a large number of women. The study of heregulin and its co-expression with erbB-2/4 receptor and the assessment of its involvement in the progression from the in situ stage of breast tumors to the invasive one will additionally increase the relevance of heregulin as a prognostic/diagnostic factor. We believe that our studies provide new insights into breast cancer diagnosis, prognosis, and treatment.
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PMID:The significance of heregulin in breast cancer tumor progression and drug resistance. 882 23

Seventy-seven men with histologically proven and newly diagnosed prostate cancer we investigated for the presence of bcl-2 protein overexpression and p53 protein accumulation 1 immunohistochemistry. Forty-five men had evidence of locally advanced and metastatic disease and we treated by means of hormone manipulation. Twenty-eight patients either failed to respond to initial hormone manipulation or relapsed within 37 months from diagnosis (median 20 months). Of the 77 cancers, 37 (48% showed bcl-2 overexpression at diagnosis. Twenty-seven of those were treated with androgen ablation and 2 (74%) had hormone-refractory disease (P = 0.0128). Twenty-three of 77 men (29.8%) had nuclear staining for p53 protein. Twenty-one of those were treated with hormone manipulation and 14 (66.6%) showed hormone resistance (P = 0.0012). Seventeen patients had both bcl-2 overexpression and p53 protein accumulation, 16 of whom were hormonally treated, with 13 (81.2%) having hormone-refractory disease (P < 0.0001). These findings suggest that the combined detection of p53 protein accumulation and bcl-2 overexpression may be useful in predicting hormone resistance in prostate cancer. By deregulating programmed cell death, alteration in these genes may prevent patients from responding to androgen ablation, or allow them to escape hormonal control of the disease.
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PMID:bcl-2 overexpression combined with p53 protein accumulation correlates with hormone-refractory prostate cancer. 888 14

Death in circulation is one of the natural barriers preventing dissemination of tumor cells and formation of metastases. One of the negative factors acting in circulation is the loss of cell contact with natural substrate which can be imitated in vitro by the incubation of cells in suspension or in semi-solid media. Normal mouse fibroblasts (MEFs) stay viable in suspension and undergo p53-independent G1 growth arrest. Transformation with Ela and ras oncogenes leads to the abrogation of this arrest and to the p53-dependent apoptosis occurring in G1 phase of the cell cycle. Suppression of apoptosis by p53 gene knock-out, transduction of dominant negative p53 mutant or bcl-2 prevents death in suspension and greatly induces frequency of colony formation in semi-solid media. The ability of cells to undergo apoptosis does not correlate with their tumorigenicity in nude mice but does correlate with their ability to survive in lungs of intravenously injected mice and to form experimental metastases. We suggest that abrogation of a p53-mediated apoptosis facilitates experimental metastasis by promoting survival of tumor cells in circulation.
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PMID:p53 modulation of anchorage independent growth and experimental metastasis. 889 17

Cytotoxic drugs currently remain as the basis for the chemotherapy of metastatic cancer. Why they fail to kill sufficient tumour cells in the major human solid cancers, such as the carcinomas, is suggested in this review to be due to the inherent inability of these cells to engage apoptosis after drug-induced damage. As a paradigm for drug resistant cancers, the resistance of bladder carcinoma cell lines to DNA damaging drugs is described here in terms of their response to the topoisomerase II poison etoposide. 60%-70% of bladder carcinomas have mutant p53; this can prevent the detection of and response to DNA damage. In vitro studies with a bladder carcinoma cell line containing a wild type p53 showed that it underwent a G1 checkpoint after etoposide, potentially allowing DNA damage repair, as well as apoptosis. In lines with mutant or non-functional p53 there is no checkpoint and no apoptosis. All lines showed constitutive expression of bcl-2 and bcl-XL (the suppressors of apoptosis) with low and non-inducible levels of bax (a promoter of apoptosis). Taken together, this menu of gene expression is more favourable to survival than apoptosis after the imposition of drug-induced DNA damage and may contribute to their inherent drug resistance.
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PMID:Apoptosis and cancer chemotherapy. 895 Apr 79

Apoptosis, or programmed cell death, is responsible for deleting cells in normal tissues to maintain homeostasis after DNA damage. Apoptosis has several physiological inhibitors, one of the most important being the proto-oncogene bcl-2. An immunohistochemical study was made of bcl-2 expression in 25 squamous cell carcinomas of the larynx, in laryngeal mucosa distant from the primary neoplasm, and in lymph node metastases. The relationship between bcl-2 expression and various clinical and pathological parameters was investigated. Bcl-2 was detected in 40% of primary tumors and in 71% of lymph node metastases; it seems to be a late event in laryngeal malignant transformation. We found no statistical association between bcl-2 expression and most of the clinical and pathological parameters examined. Only tumor differentiation was related to bcl-2 expression, bcl-2 positive tumors being moderately or poorly differentiated (p < 0.02).
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PMID:[Expression of proto-oncogene bcl-2 in squamous cell carcinoma of the larynx]. 913 20


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