(1/20) Down-regulation of caveolin-1, a candidate tumor suppressor gene, in sarcomas.
Caveolae are plasma membrane microdomains that have been implicated in the regulation of several intracellular signaling pathways. Previous studies suggest that caveolin-1, the main structural protein of caveolae, could function as a tumor suppressor. Caveolin-1 is highly expressed in terminally differentiated mesenchymal cells including adipocytes, endothelial cells, and smooth muscle cells. To study whether caveolin-1 is a possible tumor suppressor in human mesenchymal tumors, we have analyzed the expression using immunohistochemistry in normal mesenchymal tissues, 22 benign and 79 malignant mesenchymal tumors. Caveolin-1 was found to be expressed in fibromatoses, leiomyomas, hemangiomas, and lipomas at high levels comparable to normal mesenchymal tissues. The expression of caveolin-1 was slightly reduced in four of six well-differentiated liposarcomas and strongly reduced or lost in three of three fibrosarcomas, 17 of 20 leiomyosarcomas, 16 of 16 myxoid/round cell/pleomorphic liposarcomas, five of eight angiosarcomas, 15 of 18 malignant fibrous histiocytomas, and eight of eight synovial sarcomas. The immunohistochemical findings were confirmed by Western blot analysis in a number of tumors. High levels of both the 24-kd [alpha]- and the 21-kd [beta]-isoform of caveolin-1 were detected in the nontumorigenic human fibroblast cell line IMR-90. In contrast, in HT-1080 human fibrosarcoma cells, caveolin-1 is strongly down-regulated. We show that the [alpha]-isoform of caveolin-1 is potently up-regulated in HT-1080 cells by inhibition of the mitogen-activated protein kinase-signaling pathway with the specific inhibitor PD 98059, whereas the specific inhibitor of DNA methylation 5-aza-2'-deoxycytidine only marginally up-regulates caveolin-1. In addition, re-expression of caveolin-1 in HT-1080 fibrosarcoma cells potently inhibited colony formation. From these we conclude that caveolin-1 is likely to act as a tumor suppressor gene in human sarcomas. (+info)
(2/20) Evidence by spectral karyotyping that 8q11.2 is nonrandomly involved in lipoblastoma.
We report two cases of lipoblastoma with chromosome 8-related aberrations, ie, a 92,XXYY,t(7;8Xp22;q11.2)x2 /46,XY in Case 1 and a 46,XY,-8,-13,add(16) (q22),+mar, +r [cp13]/46,XY in Case 2. Using spectral karyotyping and fluorescence in situ hybridization techniques, the karyotype of Case 2 was redesignated as 46,XY, r(8), del(13)(q12), der(16)ins(16;8)(q22; q24q11.2)[cp13]/46,XY. This report delineates a new chromosome rearrangement, ie, der(16)ins(16;8)(q22; q24q11.2) in lipoblastoma, and also confirms the t(7; 8)(p22;q11.2), reported only once previously, as a recurrent translocation involved in such a tumor. These findings provide valuable information for clinical molecular cytogenetic diagnosis of lipoblastoma. Furthermore, this report highlights the value of cytogenetic and molecular cytogenetic analysis in differential diagnosis of childhood adipose tissue tumors and adds to the number of lipoblastomas reported with chromosomal abnormalities at 8q11.2. (+info)
(3/20) Genetic and molecular abnormalities in tumors of the bone and soft tissues.
BACKGROUND: Malignant transformation requires the accumulation of multiple genetic alterations such as chromosomal abnormalities, oncogene activation, loss of tumor suppressor genes, or abnormalities in genes that control DNA repair and genomic instability. Sarcomas are a heterogeneous group of malignant mesenchymal tumors of difficult histologic classification and strong genetic predisposition. This article provides a comprehensive review of the cytogenetic abnormalities observed in bone and soft-tissue tumors, emphasizing known downstream molecular changes that may play a role in oncogenesis. METHODS: The database of the National Library of Medicine was searched for literature relating to genetic and molecular mechanisms in sarcomas in general and in each of the main tumor entities. RESULTS: Recent techniques in chromosome analysis and molecular cytogenetics have improved our ability to characterize genetic changes in mesenchymal tumors. Some changes are so characteristic as to be virtually pathognomonic of particular histologic types, while others are complex, difficult to characterize, and of unknown relevance to pathogenesis. The implications to the cell of some of these abnormalities are now being recognized. CONCLUSIONS: The study of sarcomas will benefit from the information derived from genetic studies and translational research. The human genome project and new methodologies, such as computer-based DNA microarray, may help in the histogenetic classification of sarcomas and in the identification of molecular targets for therapy. (+info)
(4/20) Leptin and leptin receptor mRNA are widely expressed in tumors of adipocytic differentiation.
Adipose tissue is the principal source of leptin, a cytokine-like peptide with many biologic functions. Leptin binds to the leptin receptor, present in the hypothalamus and in many other tissues, and modulates energy balance and maintenance of body weight. The expression of leptin and leptin receptor in tumors of adipocytic differentiation has not been previously examined. Because normal adipose tissue is the principal source of leptin and expresses leptin receptor, we hypothesized that tumors of adipose tissue differentiation may also express leptin and/or the long functional form of the leptin receptor (OB-Rb). Leptin and OB-Rb were analyzed by immunohistochemistry, in situ hybridization, RT-PCR, and western blotting in 21 lipomas, 2 hibernomas, and 16 liposarcomas. Immunostaining and in situ hybridization showed leptin and OB-Rb mRNA expression in all cases of lipomas, hibernomas, and liposarcomas, including dedifferentiated and pleomorphic liposarcomas. RT-PCR analysis showed leptin and OB-Rb mRNA in both lipomas (n = 5) and liposarcomas (n = 5). Western blotting identified the 16 kDa leptin protein in a lipoma and a liposarcoma. No important difference in the expression of leptin and OB-Rb mRNA was found between lipomas and liposarcomas, although the level of leptin protein was higher in a lipoma than a liposarcoma by western blotting. These results show for the first time that leptin and OB-Rb mRNA are expressed in lipomas, hibernomas, and liposarcomas. The presence of leptin and its receptor may provide new insights into the pathobiology of these tumors. (+info)
(5/20) Adrenal lipomatous tumours: a 30 year clinicopathological experience at a single institution.
AIMS: Fatty tumours of the adrenal gland are uncommon and their features have received little attention in the literature. The aim of this study is to analyse the features of adrenal lipomatous tumours. METHODS: The histological features of primary adrenal tumours reported over a 30 year period (1970 to 1999) in Queen Mary Hospital, Hong Kong were reviewed and the clinicopathological features of adrenal lipomatous tumours were analysed. RESULTS: Adrenal lipomatous tumours were noted in 20 patients (12 men, eight women), and they accounted for 4.8% of the primary adrenal tumours reported. The adrenal fatty tumours comprised 11 myelolipomas, three lipomas, three teratomas, two angiomyolipomas, and one liposarcoma. Calcification or bone was noted in one third (seven of 20) of the adrenal tumours. In some fatty tumours (myelolipoma and angiomyolipoma), the fatty component may be inconspicuous. This is the first report in the English literature of angiomyolipoma and liposarcoma of the adrenal gland. CONCLUSIONS: Different types of fatty tumours were noted in the adrenal gland. A high index of suspicion should be maintained with an aim of surgical treatment for selected patients with large and symptomatic adrenal lipomatous lesions. Histological confirmation is needed for diagnosis. (+info)
(6/20) Caveolin expression is common among benign and malignant smooth muscle and adipocyte neoplasms.
The caveolins belong to a newly described group of membrane-scaffolding proteins. Their presence in benign endothelial cells has been used to discriminate benign from malignant vascular neoplasms. The extent of caveolin expression in cutaneous mesenchymal neoplasms has not yet been evaluated, and thus the diagnostic utility of these antibodies is not yet known. In our study, we immunohistochemically examined a spectrum of tumors derived from smooth muscle and adipocytes for caveolin expression. We found that both benign and malignant smooth muscle tumors and tumors comprised of adipocytes expressed caveolins. The presence of this protein in a range of mesenchymal neoplasms is important to know about as this decreases the reported specificity of a positive finding. It is doubtful that caveolin down-regulation contributes to the pathogenesis of liposarcomas and leiomyosarcomas. This finding also may suggest a common origin between endothelial cells and other mesenchymal cells. (+info)
(7/20) Lipoma excision.
Lipomas are adipose tumors that are often located in the subcutaneous tissues of the head, neck, shoulders, and back. Lipomas have been identified in all age groups but usually first appear between 40 and 60 years of age. These slow-growing, nearly always benign, tumors usually present as nonpainful, round, mobile masses with a characteristic soft, doughy feel. Rarely, lipomas can be associated with syndromes such as hereditary multiple lipomatosis, adiposis dolorosa, Gardner's syndrome, and Madelung's disease. There are also variants such as angiolipomas, neomorphic lipomas, spindle cell lipomas, and adenolipomas. Most lipomas are best left alone, but rapidly growing or painful lipomas can be treated with a variety of procedures ranging from steroid injections to excision of the tumor. Lipomas must be distinguished from liposarcoma, which can have a similar appearance. (+info)
(8/20) MR imaging of a posterior mediastinal ganglioneuroma: fat as a useful diagnostic sign.
We report a case of a ganglioneuroma that was found incidentally on a CT of the abdomen in a 27-year-old woman with gastrointestinal symptoms. The tumor, though located in the posterior mediastinum, demonstrated an unusual feature of abundant adipose tissue on MR imaging. The mass was later resected, and adipose tissue intermixed within a ganglioneuroma was identified microscopically. Adipose tissue is a rare finding in a ganglioneuroma, but this radiographic feature may be useful in the evaluation of posterior mediastinal masses. (+info)