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)

Histopathologic features alone fail to reliably stratify patients with clinical Stage A nonseminomatous germ cell tumors of the testis into groups with high and low risk for occult metastatic disease. Previous flow cytometric studies at Indiana University demonstrated a significant correlation between high proliferative activity and metastatic disease. The current study evaluated the prognostic significance of immunohistochemical markers related to tumor proliferation and aggressiveness in a consecutive series of clinical Stage A nonseminomatous germ cell tumors patients who underwent retroperitoneal lymph node dissection. Archival material of the orchiectomy specimens of 62 patients (45 pathologic Stage A, 17 with metastatic disease) was reviewed and immunohistochemically stained for Ki-67 antigen (MIB-1), proliferation-associated nuclear antigen (PC10), p53 protein (Pab1801), and Factor-VIII-related antigen (neovascularization). Staining with MIB-1 was significantly higher in the metastatic group (mean 80.2%, standard deviation [SD] 15.5) than in pathologic Stage A cases (66.3%, SD 27.9; P = 0.0032) and was predictive of metastatic status with a sensitivity of 82% and specificity of 69%. In this study, no patient with a MIB-1 value less than 52% had metastases. Proliferation-associated nuclear antigen and p53 staining correlated with MIB-1 values (R = 0.63 and 0.55, respectively) but did not correlate with metastatic status. Tumor angiogenesis was also not predictive of metastatic status. Assessment of proliferation rates using MIB-1 antibody in clinical Stage A nonseminomatous germ-cell-tumor patients may prove helpful in predicting metastatic status.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prognostic significance of immunohistochemical proliferation markers (Ki-67/MIB-1 and proliferation-associated nuclear antigen), p53 protein accumulation, and neovascularization in clinical stage A nonseminomatous testicular germ cell tumors. 754 14

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

Traditional histopathological risk factors have failed to predict pathological stage accurately in clinical stage I nonseminomatous testicular germ cell tumours. Histopathology, flow cytometry, cytophotometry, and immunohistochemical staining techniques were used in an effort to define high- and low-risk groups for occult metastasis in a consecutive series of 105 patients who underwent retroperitoneal lymph node dissection. After multiple logistic regression analysis, the proliferative S + G2M cell cycle fraction of the aneuploid tumour stemline was the most highly predictive parameter of pathological stage (P = 0.0004). Using a cut-off of 41%, pathological stage II patients were predicted with a sensitivity of 71%. There were 61 patients with S + G2M values below 41%, and 43 of them had pathological stage I disease (negative predictive value 87%). A low volume of embryonal carcinoma was predominant in low-risk patients, and MIB-1 immunohistochemical staining identified a subgroup of 23% of patients with pathological stage I disease and at extremely low risk of metastatic disease. Assessment of tumour cell proliferation does not allow accurate classification of high-risk patients at a level that is adequate for clinical application. Patients who are at low risk of metastasis, however, can be identified by flow cytometry, immunohistochemical proliferation markers and volume of embryonal carcinoma with 90% certainty. These parameters deserve further study, since identification of a subgroup of patients at extremely low risk of metastasis could potentially reduce the overall morbidity in the management of clinical stage I nonseminomatous testis cancer.
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PMID:[New parameters for prediction of pathological stage in clinical stage I non-seminomatous testicular tumors]. 767 41

The BCL-2 gene is the prototype of a newly described family of oncogenes involved in tumorigenesis by blocking apoptosis, or programmed cell death. Overexpression of BCL-2 protein was originally described in follicular B-cell lymphomas bearing the 14;18 translocation. BCL-2 overexpression has also been described in other lymphomas and more rarely in neoplasms outside the lymphoid tissue. The aim of this paper is to determine the immunohistochemical expression of BCL-2 in intradermal nevi and primary invasive and metastatic melanoma. Formalin-fixed and paraffin-embedded tissues from 4 cutaneous melanoma metastases, 10 primary invasive melanomas, and 10 intradermal melanocytic nevi were immunolabeled with monoclonal antibodies directed against BCL-2 protein (Dako, clone 124) and Ki-67 antigen (Amac, clone MIB-1), after antigen retrieval techniques. Morphologically normal epidermal melanocytes expressed BCL-2, as did nevi and melanomas in virtually all cells. However, whereas the labeling in normal melanocytes and nevus cells showed a uniformly strong reactivity, melanoma cells showed a variable but mainly weak reactivity. Ki-67 antigen expression was restricted to melanomas. The widespread expression of BCL-2 suggests that this oncoprotein cannot be involved in the malignant transformation of melanocytic cells. It seems likely that the decreased BCL-2 expression detected in melanomas may reflect one further step of tumor progression in melanocytic neoplasms.
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PMID:Immunohistochemical expression of BCL-2 in melanomas and intradermal nevi. 786 49

A new monoclonal antibody prepared against a fragment of Ki-67 antigen MIB, from Dianova, was applied for investigation of malignant melanomas of facial skin (25 cases) and the oral cavity (25 cases), which were routinely embedded in paraffin. The values of the Ki-67 index (expressed as a percentage of positive nuclei) were correlated with TNM characteristics of tumors and patient survival. Significant correlation was found between the Ki-67 index and the level of lymph node involvement (N value), the presence of distant metastases and the time of patient survival. A positive relationship between the Ki-67 value and tumor size was also observed although it lacked statistical significance.
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PMID:An application of MIB antibody to the retrospective study of melanomas of oral mucosa and facial skin. 813 62

The potential therapeutic efficacy of TP5 in patients with cutaneous and subcutaneous metastases of melanoma was tested in a double-blind study comparing the drug and placebo injected perinodularly. Of the 47 nodules present in the 16 patients treated with TP5, 24 showed a measurable response, whereas only one out of 15 nodules in patients treated with a placebo showed a minor response (P = 0.02). In two patients treated with TP5 a response of two nodules not perinodularly injected was also observed. Sclerosis, CD45RO+ cells and MIB 1- cells were more frequently observed in nodules treated with TP5 than with placebo. (P = 8 x 10(-4); 0.03 and 0.01, respectively). Evaluating the trends of these findings in nodules treated with placebo; with TP5-treated, non-responding nodules; or with TP5-treated, responding, a positive trend was observed for sclerosis and CD45RO+ cells (P = 5 x 10(-4) and 2 x 10(-3), respectively) and a negative one for MIB 1 cells (P = 2 x 10(-3)). These preliminary data suggest that lymphoid cells associated with nodules regression are activated large lymphocytes (CD45RO+ and CD3-). Sclerosis might be interpreted as the final morphologic event, and reduction of proliferative activity (MIB 1- cells) as the consequence of cytolytic action.
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PMID:Perinodular injection of thymopentin (TP5) in cutaneous and subcutaneous metastases of melanoma. 816 86

Abnormal patterns of proliferation characterize the behavior of many tumors. Proliferating cell nuclear antigen (PCNA) and Ki-67 are two cell cycle antigens which are expressed in proliferative states. Our study examines the prognostic value of these cell-cycle antigens in soft tissue sarcoma (STS). Paraffin-embedded primary tumor tissues from 185 patients (1980-92) were stained with the anti-PCNA antibody PC-10; 182 of these were stained with the antibody MIB-1 for Ki-67. Using PCNA (< or = 50; > 50%) and Ki-67 (< or = 10; > 10%) indices, we examined and compared metastasis-free survival (MFS) in a mixed-histotype group, as well as after subdivision into MFH and non-MFH groups. Fifty-seven patients developed metastases. The median follow-up for survivors was 6 (2-13) years. In the mixed series, the 2-year MFS for a PCNA index < or = 50 was 76%, and for an index > 50 56%. Survival predicted by Ki-67 index was comparable. PCNA index (but not Ki-67) strongly correlated with the incidence of metastasis in MFH tumors and predicted 2-year MFS of 81 vs 48%. In contrast, Ki-67 index (but not PCNA) strongly correlated with metastasis in non-MFH tumors and predicted 2-year MFS survival of 90 vs 45%. No correlation existed between PCNA and Ki-67 indices in the mixed histotype, MFH or non-MFH groups. In combination, a high PCNA and Ki-67 index correlated with poor survival, a high PCNA and lower Ki-67 index (or vice versa) with an intermediate survival, and low PCNA and Ki-67 indices with the best survival. The pattern of PCNA and Ki-67 expression raises the possibility of histotype specificity.
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PMID:Expression of proliferating cell nuclear antigen (PCNA) and Ki-67 in soft tissue sarcoma. Is prognostic significance histotype-specific? 854 44

Alterations in the tumor-suppressor gene p53 are common in many types of human malignancies, but the potential role of p53 in the pathogenesis of cutaneous melanoma is controversial. The gene product, p53 protein, is normally present in very small amounts in noncancerous tissues. Missense mutations lead to accumulation of mutant p53 in the cells, which makes it detectable immunohistochemically in many cancers. Formalin-fixed, paraffin-embedded sections of 14 primary invasive melanomas, 3 cutaneous melanoma metastases, and 10 predominantly intradermal melanocytic nevi were reacted with a panel of three anti-p53 monoclonal antibodies (mAbs) (PAb240, PAb1801, and DO7) and a mAb against Ki-67 (MIB-1), a marker of cellular proliferation. p53 was not detected in morphologically normal epidermal melanocytes or nevus cells. A single primary invasive melanoma, having a very high index of proliferation (Ki-67 expression in > 50% of cells), had diffuse nuclear labeling with all three anti-p53 mAbs used. Abnormalities of p53 expression occur rarely in cutaneous melanomas, but overexpression of p53 may occur in a subset of melanomas with a high index of proliferation.
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PMID:p53 expression is rare in cutaneous melanomas. 860 Jul 97

The spectrum of neuroendocrine lung tumours ranges from highly aggressive small cell carcinomas (SCLC) to carcinoid tumours (CD) of low malignant potential. Between these two extremes, the 'well-differentiated neuroendocrine carcinomas' (WDNEC) form a transitional group with uncertain biological behaviour. This study investigated the prognostic value of the proliferation marker MIB-1 (paraffin Ki-67) in 59 neuroendocrine lung tumours (32 SCLC, 13 WDNEC, 14 CD) by immunostaining of routinely processed paraffin sections. Morphometric evaluation was done by semi-automatic image analysis. The results were compared with survival data (mean follow-up: 42 months). The proliferation rates of the tumours as determined by MIB-1 immunoreactivity (MIB-1-PR) were significantly different between the tumour types (SCLC > WDNEC > CD) and showed a strong inverse correlation with survival time. In CD, the percentage of MIB-1-labelled nuclei never exceeded 1.1 per cent; higher values would therefore favour the diagnosis of WDNEC over that of CD. Among WDNEC, MIB-1 was able to differentiate a subgroup with excellent prognosis (MIB-1-PR: 0.3-3.4 per cent) from another subgroup with a death rate of 50 per cent (MIB-1-PR: 7.3-20.3 per cent). Within each tumour type, all patients without distant metastases at diagnosis survived when MIB-1-PR was < or = 9.4 per cent, suggesting a potential threshold for prognosis. Although the status of metastases are complementary prognostic indicators and are best used in combination to characterize the biological behaviour of neuroendocrine lung tumours.
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PMID:Prognostic value of MIB-1 in neuroendocrine tumours of the lung. 869 18

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


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