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)

The mammalian immune system is essential for surviving challenge infections with a great range of potential pathogens. The protective effect produced is dependent on many different types of cells which require flexible and independent production and regulation. In particular, many important responses are carried out by lymphocytes, which recognise foreign antigen through exquisitely specific receptors: i.e. surface immunoglobulin (sIg) on B lymphocytes and the T cell receptor (TCR) on T lymphocytes. Each lymphocyte displays receptors with a single specificity, allowing cells with particular specificities to be regulated independently. Since millions of different Igs and TCRs are expressed, the precise selection and regulation of each T and B cell population to produce a useful self-tolerant repertoire is a very complex process. Control of cell populations can, in theory, be exercised at a number of levels, including modulation of active cell death by apoptosis. Recent research has demonstrated that regulation of apoptosis is indeed a crucial element in the control of the immune system in general, and in the development of the TCR and Ig repertoires in particular. The molecular analysis of apoptosis now takes a high priority and the proto-oncogene bcl-2 appears to be responsible for specific suppression of apoptosis in several important situations. It is also clear that malfunctions affecting apoptosis, and in particular bcl-2, can result in significant progression towards malignancy.
Cancer Metastasis Rev 1992 Sep
PMID:Apoptosis in the development of the immune system: growth factors, clonal selection and bcl-2. 139 95

We report 25 cases of a peculiar sclerosing epithelioid variant of fibrosarcoma (SEF) simulating an infiltrating carcinoma. The tumors occurred primarily in the deep musculature and were frequently associated with the adjacent fascia or periosteum. The patients' ages were 14 to 87 years (median, 45). Fourteen were male and 11 female. The tumors were located in the lower extremities and limb girdles (12 cases), trunk (9), upper limb girdles (2), and neck (2). They measured 2 to 14.5 cm in greatest dimension (median size, 7 cm) and were gray to white and firm. Histologically, the lesions were characterized by a proliferation of rather uniform, small, slightly angulated, round to ovoid epithelioid cells with sparse, often clear cytoplasm arranged in distinct nests and cords. In all cases there was prominent hyaline sclerosis, sometimes reminiscent of osteoid or cartilage and foci of conventional fibrosarcoma. Occasional myxoid zones with cyst formation and foci of hyaline cartilage, calcification, and metaplastic bone were also seen. Mitotic figures were generally scarce. Vimentin was detected in 13 of 14 cases, epithelial membrane antigen in seven, S100 protein in four, and neuron-specific enolase in two. Cytokeratins were detected with AE1/AE3 and CAM 5.2 in two cases. Leukocyte common antigen, CD68 antigen, HMB45, desmin, and alpha-smooth muscle actin were negative in all cases. In 13 of 14 cases, 75% or more of the cells stained for proliferating cell nuclear antigen (PCNA). Ki67 immunostaining with MIB 1 showed low proliferative activity in all cases, averaging 5% of tumor cells or less. In all cases, p53 was detected by immunohistochemical methods; bcl-2, an antiapoptosis marker, was detected in more than 90% of the cells in 11 of 12 cases. Ultrastructurally, both the epithelioid and spindled tumor cells had features of fibroblasts. Follow-up in 16 cases ranging from 13 months to 17 years 3 months (median, 11 years 4 months) revealed persistent disease or local recurrences in 53% of patients and metastases in 43%. The metastases were to the lungs (4 cases), skeleton (3), chest wall/pleura (3), pericardium (1), and brain (1). Four patients died of disease, four were alive with disease, two were known to be alive but disease status unknown, and six had no evidence of further disease at last follow-up. The data suggest that SEF is a relatively low-grade fibrosarcoma; yet it is fully malignant despite the presence of histologically benign-appearing foci. The proliferation markers PCNA and Ki67 did not correlate with prognosis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Sclerosing epithelioid fibrosarcoma. A variant of fibrosarcoma simulating carcinoma. 766 Dec 86

Non-small-cell lung cancer (NSCLC) prognosis is strictly related to well-established clinicopathological parameters which have unfortunately become insufficient in the prognostic evaluation of this type of cancer. As p53 and bcl-2 gene deregulations are frequently involved in several types of epithelial malignancies, we investigated the Bcl-2 and p53 protein expression in 91 and 101 cases of NSCLC respectively. The expression was then compared with established indicators of prognosis and biological behaviour of the tumours. No relationship was observed between Bcl-2 and either clinicopathological or biological parameters such as histology, grading, tumour status, nodal metastasis and proliferative activity evaluated by scoring proliferating cell nuclear antigen expression and Ki-67 immunoreactivity. However, the mean Bcl-2 expression was significantly lower in patients who developed metastasis during follow-up or died of metastatic disease (P = 0.006 and P = 0.01 respectively). Moreover, survival probability was higher in patients who expressed the Bcl-2 protein (P = 0.0002). In contrast with this, p53 protein accumulation was observed in tumours with metastatic nodal involvement (P = 0.02) or in patients who developed metastasis during follow-up (P = 0.01), although no correlation was found between p53 expression and overall survival. An inverse relationship was also found between Bcl-2 and the anti-oncogene protein product p53 (P = 0.01). Thus, a high proportion of NSCLCs express p53 and Bcl-2 proteins and their expression may have prognostic importance.
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PMID:Bcl-2 protein: a prognostic factor inversely correlated to p53 in non-small-cell lung cancer. 773 90

Since the discovery of bcl-2 proto-oncogene in follicular lymphomas, the protein product has been detected in a variety of normal tissues including skin, where it is expressed in basal keratinocytes. Recent studies indicate that bcl-2 protein is detected in nonlymphoid malignancies such as neuroblastoma and carcinomas of the lung and prostate. This study investigates the presence of bcl-2 protein in benign and malignant melanocytic neoplasms of the skin. Immunohistochemical analysis of bcl-2 protein expression was performed on 39 nevi and 60 malignant melanomas, including 21 metastases. There was diffuse strong immunopositivity for bcl-2 protein in 100% of nevi and 65% (43/60) of primary and metastatic melanomas. bcl-2 protein was diffusely expressed in 67% (30/39) of primary melanomas and 54% (11/21) of metastases. Although bcl-2 immunoreactivity was observed in all levels of primary cutaneous malignant melanomas, in 43% (9/21) of deep melanomas (Clark level > or = III), and 100% (7/7) of thick tumors (thickness > or = 4.00 mm), there was focal loss of immunoreactivity. Metastatic melanomas showed focal loss of bcl-2 expression in 10% (2/21) of cases and total loss of bcl-2 protein in 39% (8/21). We conclude from our results that bcl-2 protein is expressed by benign and malignant melanocytic tumors of the skin, but there is loss of bcl-2 protein expression with increasing tumor progression.
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PMID:bcl-2 protein expression in melanocytic neoplasms of the skin. 777 75

Neoplastic development partly depends on a balance between cellular proliferative activity and the eventual suppression of the mechanism of apoptosis. Proliferative activity can be estimated by quantification of KI-67 antigen that appears during phases G1, S, G2 and M of the cellular cycle, whereas apoptosis is shown by the expression of the bcl-2 protein. In this study the expression of KI-67 and bcl-2 antigens was examined in a series of 97 gastric adenocarcinomas, to find out their relations with different clinical and pathological factors. The results showed that the expression of KI-67 was only associated to histological grade and did not have any prognostic significance. On the other hand, there was a better 5 year survival rate when invasion did not go beyond the muscularis propria, there were no lymph node metastases, in the woman and when tumors were located in the antrum. bcl-2 protein was surprisingly negative in all cases albeit of previous descriptions of overexpression of this protein in cases of gastric dysplasia. It is postulated that expression of bcl-2 could appear at an early stage of gastric carcinogenesis and that only a small proportion of malignant tumors would maintain that overexpression.
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PMID:[Expression of MIB-1/KI-67 and bcl-2 in gastric carcinoma. Relationship with clinico-pathological factors]. 852 62

The progression of prostatic adenocarcinoma from localized disease to metastatic carcinoma appears to be a multi-step sequence. The expression of common oncogenes/oncosuppressor genes and the mediating effect of neuroendocrine tumor cells may play a role in this progression. The expression of the more frequently investigated oncogenes/oncosuppressor genes (p53, c-myc, c-erbB-2, bcl-2) and the presence of neuroendocrine cells were assessed in prostatic cancer tissue from patients with localized and metastatic cancer. These oncogenes/oncosuppressor genes were evaluated according to tumor stage and grade and their relationship to one another. Grade was not related to any of the oncogene markers or to the presence of neuroendocrine cells. Advancing stage was associated with a significant increase in p53 expression, while other markers remained constant in all stages. Neuroendocrine cells, p53, c-myc, c-erbB-2 and bcl-2 were rarely co-expressed at any stage of prostate cancer.
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PMID:Immunohistochemical detection of oncogene proteins and neuroendocrine differentiation in different stages of prostate cancer. 853 88

The expression of intercellular adhesion molecule 1 (ICAM-1), a molecule pivotal in many inflammatory and immune paracrine interactions, has been highly correlated with malignant melanoma (MM) progression. Because numerous parallels exist between tissues of neural crest origin and the immune system in the regulation of postmitotic cell survival, ICAM-1 expression was studied in MM and compared with that of B-cell lymphoma/leukemia 2 protein (bcl-2 oncoprotein), an important regulator in prolonging lymphoid cell survival by blocking programmed cell death. Frozen sections from 33 cases were studied by immunoperoxidase techniques: 14 primary MM (five in situ), nine metastatic MM (one epidermotropic), four melanocytic nevi, and six normal skin controls. The percentages of the cells that stained and their intensities (0-4+) were graded. Both ICAM-1 (90%, 3-4+) and bcl-2 (95%, 2-4+) were strongly expressed in all nine metastases, including the epidermotropic disease extension. Bcl-2 strongly decorated the tumor cells in all 14 cases of primary MM (80%, 2-4+); in the five in situ MM, bcl-2 stained the atypical melanocytes at the dermal-epidermal junction (DEJ) and throughout the epidermis (75%, 1-2+). In contrast, ICAM-1 was negative in the in situ MM. ICAM-1 expression became strong (85%, 2-4+) in the dermal component of early invasive disease. Both ICAM-1 and bcl-2 were expressed in melanocytic nevi, decreasing in intensity deep within the dermis as the nevus cells senesced ("matured"). Only bcl-2 was expressed in the normal melanocytes of the six skin controls. These data show that bcl-2 is constitutively expressed in normal melanocytes and melanocytic nevi and persists in the transformed cells of early and late MM. ICAM-1 is expressed only after dermal involvement occurs, both in melanocytic nevi and in invasive MM; it persists in metastatic disease. The coexpression of bcl-2 and ICAM-1 demonstrates another similarity between the immune and neural crest systems, but it does not define or necessarily imply any functional interaction between the two proteins. The intercellular relationship of these two molecules, if any, remains to be investigated.
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PMID:Intercellular adhesion molecule 1 (ICAM-1) and bcl-2 are differentially expressed in early evolving malignant melanoma. 859 46

Carcinoembryonic antigen (CEA) has been detected by immunohistochemistry in breast carcinoma, but its relationship with prognosis is still unclear. This difficulty may be because of the great variety of antibodies used for its determination. In the present study, 271 stages I and II breast carcinomas are analyzed by immunohistochemistry, using T84.66 antibody, a well-known highly specific CEA antibody. The results show that CEA expression was not associated with any of the clinicopathologic factors analyzed. Factors associated with disease-free survival (DFS) after univariate logistic regression analyses were tumor size smaller than 2 cm (P = .01), lymph node free of metastases (P = .0000), low nuclear grade (P = .007), absence of c-erbB-2 overexpression (P = .02), and bcl-2 (P = .005) and CEA expression (P = .005), whereas those significantly associated with a better overall survival (OS) were tumor size small than 2 cm (P = .002), lymph node free of metastases (P = .0001), low nuclear grade (P = .01), low histological grade (P = .02), absence of c-erbB-2 overexpression (P = .002) and bcl-2 expression (P = .01). After multivariate stepwise regression analysis, lymph node free of metastases (P = .0000), CEA expression (P = .001), absence of c-erbB-2 overexpression (P = .01), and bcl-2 expression (P = .01) were found to be independent factors associated with DFS, whereas lymph node free of metastases (P = .0000), tumor size smaller than 2 cm (P = .0000), and absence of c-erbB-2 overexpression (P = .004) were associated with a better OS. These results show that immunohistochemical detection of CEA with the antibody T84.66 may be useful as an additional factor in establishing breast cancer prognosis.
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PMID:Carcinoembryonic antigen expression in stages I and II breast cancer: its relationship with clinicopathologic factors. 860 46

Proteins encoded by bcl-2 family genes are important regulators of programmed cell death and apoptosis. Alterations in the expression of these apoptosis-regulating genes can contribute to the origins of cancer, as well as adversely influence tumor responses to chemo- and radiotherapy. Using antibodies specific for the Bcl-2, Bax, Bcl-X, and Mcl-1 proteins in combination with immunohistochemical methods, we examined for the first time the expression of these bcl-2 family genes in 64 cases of adenocarcinoma of the prostate, including 10 Gleason grade 2 to 4 tumors, 21 grade 5 to 7 tumors, 17 grade 8 to 10 tumors, 8 lymph node metastases, and 8 bone metastases. In addition, 24 cases of prostatic intraepithelial neoplasia (PIN) or PIN coexisting with carcinoma were also evaluated. All immunostaining results were scored with regard to approximate percentage of positive tumor cells and relative immunostaining intensity. Expression of the anti-apoptotic protein Bcl-2 was present in 16 of 64 (25%) adenocarcinomas and tended to be more frequent in high grade tumors (Gleason grade 8 to 10; 41%) and nodal metastases (38%) than in lower grade (Gleason 2 to 7) primary tumors (16%; P < 0.05). Bcl-X was expressed in all 64 (100%) tumors evaluated. Bcl-X immunointensity was generally stronger in high grade primary tumors (grade 8 to 10) and metastases compared with PIN and low grade neoplasms (P < 0.0001). In addition, the proportion of specimens with > 50% Bcl-X-immunopositive tumor cells also was higher in advanced grade primary tumors (Gleason 8 to 10) and metastases than in PIN and low grade tumors (Gleason 2 to 7; P < 0.005). The anti-apoptotic protein Mcl-1 was expressed in 52 of 64 (81%) tumors, compared with only 9 of 24 (38%) cases of PIN (P < 0.001). In addition, the percentage of Mcl-1-positive cells was typically higher in Gleason grade 8 to 10 tumors and metastases than in PIN or lower grade tumors (P = 0.025). In contrast, the pro-apoptotic protein Bax was expressed in all prostate cancers evaluated, with high percentages of immunopositive cells and strong immunointensity typically occurring regardless of tumor grade. The findings suggest that expression of several anti-apoptotic members of the bcl-2 gene family, including bcl-2, bcl-X, and mcl-1 increases during progression of prostate cancers, a finding that may be relevant to the hormone-insensitive, metastatic phenotype of most advanced adenocarcinomas of the prostate.
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PMID:Immunohistochemical analysis of bcl-2, bax, bcl-X, and mcl-1 expression in prostate cancers. 862 25

A series of 60 cases of oxyphilic (Hurthle cell) carcinomas (HCC) of the thyroid were reviewed to determine whether it is possible to correlate morphologic and clinical features as a means of assessing prognosis. Twenty cases showing predominant solid or trabecular patterns (as described in poorly differentiated carcinomas with a follicular pattern) were selected and the clinicopathological features were investigated. Based on cell size, two groups of solid or trabecular HCCs were identified: The first group (17 cases) was made up of typical large granular oxyphilic cells, and the second (three cases) had small oxyphilic cells. All tumors were reactive for thyroglobulin and for a mitochondrial antigen, selectively marking oxyphilic, mitochondrial-rich cells. Nuclear pleomorphism in individual cells was a common feature, but foci of anaplastic carcinoma were never found. Four cases overexpressed p53 protein and 10 expressed bcl-2 gene product. At follow-up, among the high-stage (pT3-pT4) tumors, seven patients had recurrences or metastases, six of whom were alive with disease or died of disease. In the control group of HCC with predominant follicular patterns, only one of 40 cases had a fatal outcome. The difference was statistically significant. Small-cell patterns and a p53 protein-positive/bcl-2 gene product negative phenotype were features of clinically aggressive HCC cases. We suggest that within the spectrum of oxyphilic (Hurthle cell) tumors, poorly differentiated HCC showing solid or trabecular patterns are a distinct group, based on both morphological and clinical features.
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PMID:Poorly differentiated oxyphilic (Hurthle cell) carcinomas of the thyroid. 865 47


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