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 aim of this study was to evaluate angiogenesis in tissue of the pancreatic ductal adenocarcinoma and to correlate it with histopathological data such as tumour differentiation, tumour size, lymph node metastasis and patients survival. Tumour samples obtained during surgery from 36 patients were immunostained for the presence of blood vessels with monoclonal antibody against the CD31 molecule. Evaluation of microvasculature was perfomed by counting the microvessel density (MVD) in selected areas under light microscope as well as by computer assisted image analysis (CAIA). In the latter, the following parameters were used for assessment of microvessels: mean number/field, mean area of the vessels, total area/field and total perimeter/field. MVD values obtained under optical microscope and with CAIA were highly correlated. All parameters characterising microvasculature in CAIA also revealed a significant correlation with the histological grading of tumours; generally the less differentiated tumours manifested more extensive vascular network. No significant relationship was found between the tumour size and any of the CAIA parameters. The area of vessels (both total and mean values) revealed a significant, inverse correlation with the incidence of lymph node metastases. The same type of correlation was also found between the mean vessel area and the postoperative survival period. The results show that CAIA of microvessels offers new parameters with some predictive value for the outcome of patients with pancreatic cancer.
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PMID:Morphological parameters of the angiogenic response in pancreatic ductal adenocarcinoma--correlation with histological grading and clinical data. 1176 69

We report the seventh case of angiosarcoma of the heart in a child. The patient was a 23-month-old female who presented for lower extremity limping and underwent open surgical biopsy of the femur. Immediately postoperatively, she developed pericardial tamponade, and a bulky intracardiac mass was discovered as the underlying cause. The mass was composed of highly pleomorphic tumor cells reactive for the endothelial markers CD31, CD34, and factor VIII-related antigen (FVIII-RA). Staging evaluation revealed widespread metastases involving the brain, ovaries, and bone marrow. She died of complications of metastatic disease 8 months following initial presentation. Unusual features of this case include the young age of the patient, left-sided nature of the cardiac tumor, presentation secondary to metastatic disease, and the pattern of metastases. The literature on cardiac angiosarcoma, which is limited to six case reports in the pediatric population, is also reviewed.
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PMID:Pediatric angiosarcoma of the heart: a unique presentation and metastatic pattern. 1177 52

The aim of this study was to investigate whether tumour hypoxia and/or vascular hot spots promote the development of metastatic disease. The D-12 human melanoma xenograft line was used as a tumour model. Hypoxia and vascular hot spots were detected by immunohistochemistry using pimonidazole as a hypoxia marker and anti-CD31 antibody to visualize endothelial cells. Vascular hot spots were found to be induced in hypoxic foci, owing to hypoxia-induced up-regulation of angiogenesis stimulatory factors. This effect was mediated by interleukin 8 and possibly also by vascular endothelial growth factor. Interleukin 8 positive foci showed a high degree of co-localization with hypoxic foci, as revealed by immunohistochemistry. The incidence of spontaneous pulmonary metastases was associated with the density of hypoxic foci, the density of interleukin 8 positive foci and the density of vascular hot spots in the primary tumour. Treatment with neutralizing antibody against interleukin 8 and/or vascular endothelial growth factor resulted in hypoxia-induced necrosis rather than hypoxia-induced vascular hot spots and inhibited metastasis. Our study suggests a cause-effect relationship between hypoxia and metastasis in cancer and hence an elevated probability of metastatic disease in patients having primary tumours characterized by high densities of hypoxic foci and vascular hot spots.
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PMID:Hypoxia-associated spontaneous pulmonary metastasis in human melanoma xenografts: involvement of microvascular hot spots induced in hypoxic foci by interleukin 8. 1187 May 23

The prognostic value of the extent of neovascularization in cutaneous melanoma is a highly controversial issue. The aim of the current study was to evaluate whether the morphometric analysis of tumor vascularity may be helpful in predicting the clinical outcome of patients with thick cutaneous melanomas. A series of 15 patients with melanoma (>3 mm in thickness) who did not experience disease progression after long-term follow-up (10 years) and 30 matched controls who underwent recurrence and/or metastases were selected for the study. Microvessels were immunohistochemically stained with anti-CD31 antibody. Several parameters, including vessel number, vascular density, vessel area, equivalent circle diameter, perimeter, shape factor, compactness, and the number of vascular ramifications per 100 vessel sections, were quantitatively assessed by a computer-aided semi-automatic image analysis system. Mean vessel area was 341.69 microm2 in cases without progression and 512.55 microm2 in the progressed melanomas (P=0.008, Mann-Whitney U test). The mean equivalent circle diameter was 18.95 microm in non-progressed melanomas and 22.57 microm in progressed melanomas (P=0.009). The mean number of ramifications was 0.8 in cases without progression and 1.9 in the controls (P=0.03). Microvessel count and vascular density were higher in progressed cases (17.37 vs. 11.73 and 28.94/mm2 vs. 19.55/mm2, respectively), but the difference did not reach statistical significance (P=0.06). Our results suggest that neovascularization is a critical event in the progression of thick melanoma. Its prognostic significance is better assessed by quantification of vessel area, equivalent circle diameter, and microvessel branching, whereas microvessel count and vascular density do not provide significant prognostic information.
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PMID:Tumor angiogenesis as a prognostic factor in thick cutaneous malignant melanoma. A quantitative morphologic analysis. 1194 72

An angiogenic response originating from peritumoral sinusoids and portal tracts that leads to the formation of metastases with sinusoidal- and portal-type angiogenic patterns, respectively, occurs during the course of liver colonization by murine 51b colon carcinoma (51b-CC) cells. We found a 5-fold increase in endogenous endostatin levels from hepatic blood over baseline (25 +/- 6 ng/mL) when micrometastatic foci had a detectable size and a 14-fold increase when macrometastases were developed. Despite this endogenous endostatin production, subcutaneous administration of recombinant human endostatin (rh-E; 50 mg/kg) decreased metastasis number by 60% when dosed from days 1 to 20 after 51b-CC cell injection, by 40% when given from days 10 to 20, and by 30% when administered as a single dose 30 minutes before 51b-CC cell injection compared with controls. In addition, administration of rh-E from days 10 to 20 decreased overall metastasis volume by 90% compared with controls. rh-E increased the number of necrotic sinusoidal-type metastases by 7-fold and decreased their intrametastatic CD31(+)-microvessel density by 80% without affecting portal-type metastases. Flow cytometry showed rh-E binding to mouse liver sinusoidal cells but not to CD45(+) cells (leukocytes and Kupffer cells) or 51b-CC cells. Furthermore, rh-E induced sinusoidal endothelium cell apoptosis. In conclusion, despite the direct correlation between metastasis development and endogenous endostatin generation in the liver, administration of rh-E inhibited micrometastasis generation and macrometastasis growth very efficiently. The antiangiogenic mechanism was selective for sinusoidal-type metastases, in which the neovasculature originating from sinusoidal endothelium cells was targeted by rh-E.
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PMID:Endostatin inhibits murine colon carcinoma sinusoidal-type metastases by preferential targeting of hepatic sinusoidal endothelium. 1198 60

Tumors require a blood supply for growth and hematogenous metastases. Until recently, most research in this area has focused on the role of angiogenesis, the recruitment of new vessels into a tumor from preexisting vessels. Previously, in a study of breast cancer (IBC), in which we used established inflammatory breast cancer (IBC) xenografts (WIBC-9) originating from a patient with IBC (Shirakawa et al., Cancer Res 2001:61:445-451), we reported observing vasculogenic mimicry (VM), a condition in which bloodstreams within cancer tissue are not accompanied by a lining of endothelial cells (ECs) (Shirakawa et al., Cancer Res 2002:62:560-566). In the present study, we examined 331 surgically resected breast cancer specimens for evidence of VM, using immunohistochemistry and laser-captured microdissection (LCM) followed by nested reverse transcriptase polymerase chain reaction (RT-PCR). Surprisingly, 7.9% (26 specimens) of the 331 specimens exhibited evidence of VM. Of these 26 VM specimens, 84.6% (22 specimens) exhibited pseudo-comedo formation. RT-PCR analysis of 8 microdissected typical VM specimens revealed expression of Tie-2, Flt-1, thrombin receptor and CD31 in 63, 50, 0 and 0% of specimens, respectively. In contrast, results of RT-PCR analysis of 8 specimens from non-VM tumors were negative for expression of these genes. The 26 VM cases tended to have a higher percentage of hematogenous recurrence (p = 0.059) and a lower percentage of 5-year survival (p = 0.071) than the 305 non-VM cases. However, there were no significant differences in tumor size, lymph node metastasis, estrogen receptors or progesterone receptors between the 2 groups (p > 0.1). Our results suggest that the existence of VM increases the likelihood of hematogenous metastases and is in inverse proportion to prognosis.
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PMID:Vasculogenic mimicry and pseudo-comedo formation in breast cancer. 1211 83

Primary clear cell carcinoma of the breast is a rare tumor. The clear cell morphology of the neoplastic population in these tumors has been ascribed to the presence of intracellular lipid, mucin or glycogen, or to myoepithelial, apocrine, or neuroendocrine differentiation. However, a clear cell neoplasm exhibiting evidence of a range of differentiation has not been previously reported. We describe a case of a glycogen-rich primary clear cell breast carcinoma occurring in a 59-year-old woman that showed positivity for apocrine and neuroendocrine markers, as well as possible myoepithelial differentiation. The tumor was a 4-cm mass composed predominantly of periodic acid-Schiff-positive clear cells arranged in a solid, infiltrative pattern. Immunohistochemical staining of the tumor cells was variably positive for cytokeratin, progesterone receptors, gross cystic disease fluid protein-15, neuron specific enolase, chromogranin, and S-100 protein and negative for estrogen receptors, smooth muscle actin, CD31, and CD34. The patient refused any form of further investigation or treatment, but shows no evidence of recurrence or metastatic disease after 18 months of follow-up.
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PMID:Clear cell carcinoma of the breast with immunohistochemical evidence of divergent differentiation. 1217 Apr 58

Malignant change in a benign vascular tumor is exceedingly rare, and there have been only five previously reported convincing cases. Four new cases of angiosarcoma (AS) arising in a hemangioma/vascular malformation (HVM) are described. All patients were in the 6th or 7th decade of life (two female, two male). Development of an enlarging deep-seated mass was the main presenting symptom. MRI disclosed the presence of two separate soft tissue masses in both thighs in one patient. No patient had a history of prior radiotherapy at the same site. Preoperative duration, known in three cases, ranged from 1 to 24 months (median 12 months). Three tumors were located in the lower extremities (thigh and buttock), one in the retroperitoneum, and one in the parotid region. Three patients were treated by marginal excision; in one case only a biopsy was performed. Radiotherapy/chemotherapy was given in all cases. Two patients were disease free 2 and 14 months after surgery and two developed metastases. Grossly, the tumors were described as frankly hemorrhagic masses or as firm, whitish areas with hemorrhagic nodules and were centered in skeletal muscle in three cases. Size ranged between 2.2 cm and 8 cm (median 4.3 cm). Histologically, all the tumors had two distinct components. In three cases the benign and the malignant components were variably intermixed, whereas in one case the HVM was mainly located at the edge of the malignant tumor. The benign component showed features of an arteriovenous hemangioma (three cases) or intramuscular capillary hemangioma. AS showed epithelioid morphology in three cases and a well-differentiated dissecting pattern in one case. An imperceptible transition between the two components was noted in two cases. The two anatomically separate masses excised from one patient appeared almost identical. All cases were positive for at least two endothelial markers (CD31, CD34, VWF) and negative for the epithelial markers (EMA, AE1/AE3, Pan-keratin). Possible mechanisms for this exceptional phenomenon are discussed.
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PMID:Angiosarcoma arising in hemangioma/vascular malformation: report of four cases and review of the literature. 1236 47

Fibroblastic tissue is an important component of malignant tumors, involved in the establishment of metastatic foci from micrometastases, and thought to prevent invasion of metastatic tumor cells into surrounding tissue. However, experimental models of fibrosis during the growth of micrometastasis into established metastases were not previously available. In the present paper, we performed immunohistochemical studies on experimental hepatic metastasis with colon 38 mouse colon carcinoma cells injected into syngeneic C57BL/6 mice. Early and late stages of metastatic nodules were examined for the distribution of endothelial cells, fibroblasts, and macrophages by the use of markers of these cells. One week after intrasplenic injection of colon 38 cells, micrometastases mainly appeared in the region of sinusoids accompanied with invasion of F4/80-positive Kupffer cells. Transitional metastases can be defined based on the histological appearance and intensive infiltration of both macrophages and fibroblasts. These transitional metastases were connected by protrusions of fibroblast-rich tissues co-localized with collagen-rich matrix and CD31-positive cells. This protrusion preceded fibrosis formation characteristics to established metastases associated with angiogenesis and segregation of tumor cells from host cells. Three stages can thus be classified during the development of hepatic metastasis in this syngeneic experimental system: micrometastasis, transitional metastasis, and established metastasis.
Clin Exp Metastasis 2002
PMID:Redistribution of fibroblasts and macrophages as micrometastases develop into established liver metastases. 1249 93

We are reporting seven histologically identical cases of a distinctive, low-grade vascular tumor that closely mimics an epithelioid sarcoma because of growth in solid sheets and nests, the eosinophilia of the rounded to slightly spindled neoplastic cells, and the diffuse, strong cytokeratin expression. Termed epithelioid sarcoma-like hemangioendothelioma, all were diagnosed by the submitting pathologist or another expert consultant as epithelioid sarcoma. Although none displayed architectural evidence of vascular differentiation in the form of multicellular vascular channels, some displayed subtle cytologic features of vascular differentiation and all displayed immunohistochemical evidence of endothelial differentiation. The patients (four male; three female) ranged in age from 17 to 54 years (median 23 years). Ranging in size from 1 to 3.5 cm, they occurred in the extremities (n = 5), scalp (n = 1), and chest wall (n = 1), both in deep (n = 3) and superficial (n = 3) soft tissue or both (n = 1). The tumors were characterized by sheets, ill-defined nodules, or fascicles of deeply eosinophilic cells set within a desmoplastic stroma. Multicellular vascular channel formation and/or hemorrhage were absent in all cases. In four cases intracytoplasmic vacuolization suggestive of intracytoplasmic vascular lumen formation was noted. The typical neoplastic cell was large and rounded in shape but modulated in areas to a spindled or multipolar shape. Mitotic activity was low (<5 mitotic figures/50 high power fields), nuclear pleomorphism was mild to moderate, and necrosis was absent. The tumors were positive for cytokeratin (6 of 6), vimentin (6 of 6), CD31 (5 of 6), FLI-1 (6 of 6), but negative for CD34 (0 of 6). Within a follow-up period of 3-72 months (median 39 months), two patients experienced a local recurrence and one patient regional soft tissue metastases, but no distant ones. Two patients presented with multifocal lesions suggestive of regional metastases. Currently, two patients are alive with disease and five are disease free. Epithelioid sarcoma-like hemangioendothelioma appears to be a largely unrecognized epithelioid vascular tumor with an indolent course. Despite its similar clinical and histologic features, it differs from epithelioid sarcoma by the presence of endothelial markers and the absence to date of distant metastases. Its distinction from other epithelioid vascular lesions is discussed. We think this tumor fits best into the family of "hemangioendothelioma" or vascular lesions of intermediate malignancy.
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PMID:Epithelioid sarcoma-like hemangioendothelioma. 1250 27


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