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)

An 85-yr-old male presented with complaints of a 40-lb weight loss and a dull left upper quadrant abdominal pain. He also complained of decreased appetite, generalized weakness, generally not feeling well, and a dull left upper quadrant abdominal pain that was not relieved by food. He had a ventral and a left-sided inguinal hernia. Laboratory investigations revealed iron deficiency anemia, the cause of which was not apparent despite extensive investigation including computerized tomographic scans, esophagogastroduodenoscopy, and small-bowel follow-through examination. Surgical exploration for possible angiodysplasia, malignancy, and/or mesenteric ischemia revealed an incarcerated hernia, and the histopathological examination of the surgical specimen revealed high-grade angiosarcoma. The tumor showed strong positivity for vimentin and CD31 and a focal positivity for Factor VIII and CD34. At that time he was found to have hepatic metastases. He was started on thalidomide as an experimental measure with no change in the performance status and increasing evidence of necrosis in the metastatic lesion.
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PMID:Angiosarcoma of the small intestine: a possible role for thalidomide? 1471 38

Few data on the influence of lymphatic microvessel density (LMVD) on survival in patients with melanoma are available. The aim of this study was to assess LMVD and blood microvessel density (MVD) in tissue samples from 120 patients with melanoma. LMVD was stained with an antibody staining for podoplanin, and blood MVD was assessed by CD31 (PECAM-1)-immunostaining. Survival was determined using univariate and multivariate analysis. A significant association between a high CD31 MVD (but not LMVD) and the presence of lymph node metastases (P=0.007) was observed. Patients with a high LMVD had a significant shorter overall (OS) (P=0.0436) and disease-free survival (DFS) (P=0.0249) in univariate analysis. The survival analysis showed CD31 MVD was a strong prognostic factor for OS and DFS in both uni-and multivariate analyses. Our results demonstrate LMVD as a prognostic factor in malignant melanoma, although its prognostic relevance is much smaller compared with blood MVD.
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PMID:Selective immunohistochemical staining shows significant prognostic influence of lymphatic and blood vessels in patients with malignant melanoma. 1474 53

The natural course of tumor microvascularity in rat MTLn3 mammary adenocarcinomas was studied. The relationship between microvessel density (MVD), vascular endothelial growth factor (VEGF) expression, and histopathology was compared in primary and metastatic axillary (ALN) and inguinal lymph node (ILN) tumors over 5-6 tumor doublings. Excised tumors were examined for (i) MVD assessed by immunostaining with anti-CD31 antibody, (ii) VEGF expression assessed by immunostaining with anti-VEGF antibody, and (iii) histopathologic extent of metastatic lymph node invasion. MVD and VEGF scores rose asymptotically with increasing tumor weight in both primary and metastatic tumors. The MVD saturation level was significantly greater for primary tumors (MVD = 22) than for ALNs or ILNs (MVD = 14). Maximal VEGF score was not statistically different between the three kinds of tumors, however the rate of rise in VEGF expression was different. Near-maximal VEGF expression occurred early in tumor growth, preceding microvessel development. Both MVD and VEGF expression in lymph nodes were proportional to the pathology score characterizing increasing metastatic invasion. LNMs limited to the subcapsular sinus had the lowest MVD, indicating an ability to survive without significant vasculature. These findings underscore the differences in angiogenesis between primary tumors and LNMs and have implications for therapy of metastatic cancer.
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PMID:The natural progression of microvasculature in primary tumor and lymph node metastases in a breast carcinoma model: relationship between microvessel density, vascular endothelial growth factor expression, and metastatic invasion. 1496 8

The immunocytochemical detection of Tie-2/Tek, CD105, and CD31 was assessed in a large series (n = 905) of breast carcinomas on frozen sections. Results were correlated with patients' long-term outcome (median, 11.7 years) to define the respective prognostic significance of these markers. Univariate (Kaplan-Meier) analysis demonstrated that higher expression of CD31 (P = 0.032), CD105 (P = 0.001), and Tie-2/Tek (P = 0.025) correlated with poorer survival. However, only greater CD105 expression could significantly (P = 0.035) identify node-negative patients with poorer survival. Moreover, in multivariate analysis, CD105 and Tie-2/Tek, but not CD31, expression proved to be independent significant prognostic indicators. Marked expression of CD31 (P = 0.024), CD105 (P = 0.001), and Tie-2/Tek (P = 0.01) also correlated with higher risk of metastases in node-negative patients. It is concluded that CD105 immunoexpression in breast carcinomas is an independent prognostic indicator in node-negative patients, better in terms of overall survival than Tie-2/Tek and CD31. Also, Tie-2/Tek expression proved more sensitive than CD31 expression in terms of prognostic significance. Compared with CD31, CD105 and Tie-2/Tek have more clinical relevance for patient monitoring and also can serve as targets for specific therapy, such as CD105 immunotoxins or Tie-2/Tek pathway blockade, as recently suggested in experimental studies.
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PMID:Long-term prognostic significance of neoangiogenesis in breast carcinomas: comparison of Tie-2/Tek, CD105, and CD31 immunocytochemical expression. 1499 34

An orthotopic mouse model of cervical carcinoma has been used to investigate the relationship between acute (cyclic) hypoxia and spontaneous lymph node metastasis in vivo. The human cervical carcinoma cell line ME-180 was stably transfected to express the fluorescent protein DsRed2, which allowed the in vivo optical monitoring of tumor growth and metastasis by fluorescent microscopy. The surgically implanted primary tumors metastasize initially to local lymph nodes and later to lung, a pattern consistent with the clinical course of the disease. The effect of acute hypoxia on the growth and spread of these tumors was examined by exposing tumor-bearing mice to treatment consisting of exposure to 12 cycles of 10 min 7% O(2) followed by 10 min air (total 4 h) daily during tumor growth. After 21 days, the tumors were excised, lymph node and lung metastases were quantified, and the hypoxic fraction and relative vascular area of the primary tumors were assessed by immunohistochemical staining for the hypoxic marker drug EF5 [2-(2-nitro-1H-imidazole-1-yl)-N-(2,2,3,3,3-pentafluoropropyl) acetamide] and the vascular marker CD31, respectively. In untreated mice, the primary tumor size was directly correlated with lymph node metastatic burden. The acute hypoxia treatment resulted in a significant decrease in the size of the primary tumors at the time of excision. However, the mice in the acute hypoxia group had an increased number of positive lymph nodes (2-4) as compared with control mice (1-3). Lung metastasis was not affected. The acute hypoxia treatment also decreased the relative vascular area in the primary tumors but did not affect the hypoxic fraction. These results suggest that fluctuating oxygenation in cervical carcinoma tumors may reduce tumor growth rate, but it may also enhance the ability of tumor cells to metastasize to local lymph nodes.
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PMID:Acute hypoxia enhances spontaneous lymph node metastasis in an orthotopic murine model of human cervical carcinoma. 1502 43

Angiogenesis is necessary for the growth of primary tumors and the formation of metastases. It is well known that vascular endothelial growth factor (VEGF) and its receptors play a major role in this process. To date, the formation of bone metastases has been poorly understood. Tumor cells must interact with the microenvironment of the bone and new blood vessels must spread. The ET/ET(A) (endothelin) receptor system seems to play an important role in this process. Specimens from metastatic bone lesions and non-malignant bone tissue were analyzed by histological and immunohistochemical staining. Sections were stained with antibodies against CD31, Flt-1, KDR, endothelin-1 (ET-1) and endothelin receptor A (ET(A)). Our studies show that there is an increased microvessel density (MVD) in metastatic bone lesions from different primary tumors in contrast to normal bone tissue. In nearly all tumor formations of the bone, ET-1 and its receptor ET(A) was found by immunohistochemistry. We also performed immunohistochemical staining for the VEGF-receptors Flt-1 and KDR. In conclusion, there is an increased vessel density in metastatic bone lesions in contrast to normal bone tissue. The ET/ET(A) system can be detected in nearly all bone specimens and is upregulated in metastatic bone lesions in contrast to healthy bone tissue.
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PMID:Angiogenesis and the ET-1/ETA receptor system: immunohistochemical expression analysis in bone metastases from patients with different primary tumors. 1504 98

We describe the clinicopathologic findings in a so far unrecognized thymic tumor. The tumor occurred in a 70-year-old woman with respiratory distress but neither myasthenia gravis nor other symptoms. Metastases or another primary tumor were absent. The well-circumscribed neoplasm was located in the thymic region, measured 18 x 12 x 8 cm, and showed a homogeneous, tan-colored, soft cut surface. By histology, the tumor lacked a true capsule and a lobular growth pattern, was almost devoid of stroma, and infiltrated among remnant thymus lobules. The polygonal tumor cells formed solid sheets, trabeculae, or occurred as single cells that resembled hepatocytes. Proliferative activity was low. Portal structures, sinuses, and bile were absent as were areas of conventional thymoma, adenocarcinoma, or germ cell tumor. The tumor expressed cytokeratins 7 and 19, alpha1-antitrypsin, alpha1-antichymotrypsin, and hep-Par-1. Alpha-fetoprotein (AFP), human beta-chorionic gonadotropin (beta-HCG), placental alkaline phosphatase, CD5, CD30, CD31, CD34, CD45, CD68, CD99, S-100, HMB45, desmin, actin, or neuroendocrine markers were not expressed, and intratumorous CD1a+ or TdT+ immature T cells were absent. AFP was repeatedly undetectable in the blood. Mediastinal tumor recurrence was detected 6 months after surgery. Following radiochemotherapy, the patient has remained free of disease for 26 months. We conclude that this tumor is a thymic carcinoma (WHO type C thymoma). A diagnosis of hepatoid yolk sack tumor appears unlikely considering absence of a bona fide germ cell component, lack of AFP expression, and the patient's female gender. Because of its morphologic and immunohistochemical features, we propose the term "hepatoid thymic carcinoma" for this new type of thymic carcinoma.
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PMID:Hepatoid thymic carcinoma: report of a case. 1504 16

The purpose of this study was to investigate tumor angiogenesis in a series of benign and malignant pheochromocytomas and to determine whether there is a correlation between angiogenesis and the presence of distant metastases. In this study, the CD31 monoclonal antibody was selected to measure intratumoral microvessel density. Nineteen patients with malignant pheochromocytomas and nineteen patients with benign pheochromocytomas who underwent operation were studied. In order to quantify intratumoral microvessel density, the total number of pixels of CD31-positive reactivity was assessed and expressed as a percentage of the total tissue area in the analyzed field. Analysis of variance revealed a statistically significant correlation between malignancy and intratumoral microvessel density (p = 0.0009). Although there was a considerable variability in the intratumoral microvessel density from tumor to tumor within both the benign and the malignant group, a percentage of more than 28.5% anti-CD31 stained area was found only in malignant tumors. In conclusion, this study shows that the mean intratumoral microvessel density in malignant pheochromocytomas is increased approximately twofold as compared with benign tumors. However, the clinical significance of this prognostic marker is rather weak, because only 4 of the 19 malignant pheochromocytomas had microvessel density higher than this threshold of 28.5%.
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PMID:The significance of angiogenesis in malignant pheochromocytomas. 1506 75

Our purpose was to determine the respective prognostic significance of CD105 and CD31 immunoexpression in node negative patients with breast carcinoma, since angiogenesis induces blood borne metastases and death in carcinomas. CD105 (endoglin) has been reported as expressed by activated endothelial cells and consequently should better reflect neoangiogenesis in malignant tumors. Comparison of CD31 and CD105 immunocytochemical expression was undertaken in a series of 905 breast carcinomas. Results were compared to patients' long-term (median = 11.3 years) outcome. Univariate (Kaplan-Meier) analysis showed that the number of CD105+ microvessels (cut-off 15 vessels) correlated significantly with poor overall survival (p=0.001). This correlation was less significant in node negative patients (p=0.035). The number of CD31+ microvessels (cut-off 25 vessels) similarly correlated with poor survival (p=0.032) but not in the subgroup of node negative patients. Marked CD105 expression also correlated with a high risk for metastasis in all patients (p=0.0002) and in the subset of node negative patients (p=0.001). Similarly metastasis risk in node negative patients correlated with marked CD31 immunocytochemical expression (p=0.02). Multivariate analysis (Cox model) identified CD105, but not CD31 immunoexpression, as an independent prognostic indicator. Our results suggest that: i) in breast carcinomas, immunoselection of microvessels containing activated CD105 labelled endothelial cells is endowed with a stronger prognostic significance, as compared to CD31 vessels labelling; ii) the CD105 immunoexpression may be considered as a potential tool for selecting node negative patients with a poorer outcome and higher metastasis risk; iii) in these patients specific antiangiogenic therapy targeted by anti-CD105 conjugates can be further developed.
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PMID:Prognostic significance of angiogenesis evaluated by CD105 expression compared to CD31 in 905 breast carcinomas: correlation with long-term patient outcome. 1506 42

Kaposiform hemangioendothelioma (KH) is a rare tumor of childhood often associated with Kasabach-Merritt phenomenon (KMP) and occasionally lymphangiomatosis. Although generally considered distinct from other vascular neoplasms, its rarity has precluded a thorough study of its immunophenotypic profile and long-term behavior. Thirty-three cases of KH were reviewed and immunostained for alpha-smooth muscle actin, various endothelial markers (CD31, CD34, vWf, FLI1), a platelet marker (CD61), and the juvenile hemangioma-associated markers GLUT-1 and Lewis Y antigen (LeY). In addition, the presence of HHV-8 was evaluated by RT-PCR. The patients (20 males and 13 females) ranged in age from 2 weeks to 20 years (mean 3 years 9 months). Tumors developed on the extremities (17 cases), head/neck (8 cases), and other sites (8 cases) and affected both superficial and deep soft tissue. Those in the skin presented as slightly raised blue-red lesions. More than half of the patients presented with KMP (14 of 25). Tumors consisted of irregular, infiltrating nodules of compressed vessels, which modulated between areas resembling a capillary hemangioma and Kaposi sarcoma (KS). Endothelial cells in nodules were CD31, CD34, and FLI1 positive but negative for GLUT1 and LeY. Scattered "epithelioid" or glomeruloid islands featuring endothelium associated with clusters of plump alpha-smooth muscle actin-positive pericytes, stippled hemosiderin, and CD61-positive fibrin thrombi likely represent the morphologic sites of platelet consumption. Small and large lymphatic channels occurred in 22 of 33 cases and were typically seen peripheral or deep to the main tumor mass. HHV-8 transcripts were not identified (0 of 3 cases). Follow-up information was available in 22 patients (range 8 months to 15 years; mean 2 years) and indicated that 3 died of disease, 8 were alive with disease, and 10 were alive without residual disease. Two patients developed regional perinodal soft tissue involvement, but none developed distant metastases. KH is a lesion having both a vascular and lymphatic component. Its common association with KMP probably relates in part to unique architectural features that favor turbulent blood flow and platelet activation. KH can also be reliably separated from JH by GLUT-1 and LeY immunostaining, indicating differences in the morphologic and functional attributes of the endothelium between the two lesions. The absence of HHV-8 in KH underscores a different pathogenesis from Kaposi sarcoma. Our study, the largest to date, emphasizes that mortality is due to KMP and not metastatic disease, which appears limited to regional perinodal soft tissue. Given this behavior, its continued classification as a vascular tumor of intermediate malignancy is warranted.
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PMID:Kaposiform hemangioendothelioma: a study of 33 cases emphasizing its pathologic, immunophenotypic, and biologic uniqueness from juvenile hemangioma. 1510 42


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