0
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found

      Expression of Vascular Endothelial Growth Factor A, Matrix Metalloproteinase 9 and Extravascular Matrix Patterns in Iris and Ciliary Body Melanomas

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Purpose: It was the aim of this study to assess the expression of vascular endothelial growth factor (VEGF)-A, matrix metalloproteinase (MMP)-9 and extravascular matrix patterns (EMPs) in iris and ciliary body melanomas and their correlations with histopathologic parameters. Methods: The study was conducted on 3 iris and 15 ciliary body melanomas. All tumors were subjected to immunohistochemical techniques for VEGF-A and MMP-9 expressions, the presence of EMPs was assessed, and routine paraffin sections were stained with hematoxylin-eosin. Cell type, tumor localization, degree of pigmentation, necrosis, mitotic index, lymphocytic infiltration and sclera invasion were analyzed using light microscopy. Results: The mean patient age at the time of treatment was 43 years (range 19–69, median 39.5); 10 (55.6%) patients were males and 8 (44.4%) females. Histopathological cell types were spindle cells in 55.6%, mixed cells in 16.7%, and epithelioid cell types in 27.8% of tumors. Positive reaction for VEGF-A and MMP-9 was present in 66.7 and 72.3% of the tumors, respectively. Microvascular loops and/or networks were seen in 33.4% of the tumors, with the remaining 66.7% of tumors displaying one or more of the other patterns. Metastatic disease developed in only 1 patient during follow-up. Tumor cell type, tumor size, mitotic rate, degree of pigmentation and EMPs were not correlated with metastasis. Conclusions: This study suggests that VEGF-A and MMP-9 were positive in the majority of iris and ciliary body melanomas. No correlation was found between VEGF-A and MMP-9 immunoreactivity and EMPs and occurrence of metastases in cases of anterior uveal melanoma.

          Related collections

          Most cited references 12

          • Record: found
          • Abstract: found
          • Article: not found

          Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry.

          Tissue sections from aggressive human intraocular (uveal) and metastatic cutaneous melanomas generally lack evidence of significant necrosis and contain patterned networks of interconnected loops of extracellular matrix. The matrix that forms these loops or networks may be solid or hollow. Red blood cells have been detected within the hollow channel components of this patterned matrix histologically, and these vascular channel networks have been detected in human tumors angiographically. Endothelial cells were not identified within these matrix-embedded channels by light microscopy, by transmission electron microscopy, or by using an immunohistochemical panel of endothelial cell markers (Factor VIII-related antigen, Ulex, CD31, CD34, and KDR[Flk-1]). Highly invasive primary and metastatic human melanoma cells formed patterned solid and hollow matrix channels (seen in tissue sections of aggressive primary and metastatic human melanomas) in three-dimensional cultures containing Matrigel or dilute Type I collagen, without endothelial cells or fibroblasts. These tumor cell-generated patterned channels conducted dye, highlighting looping patterns visualized angiographically in human tumors. Neither normal melanocytes nor poorly invasive melanoma cells generated these patterned channels in vitro under identical culture conditions, even after the addition of conditioned medium from metastatic pattern-forming melanoma cells, soluble growth factors, or regimes of hypoxia. Highly invasive and metastatic human melanoma cells, but not poorly invasive melanoma cells, contracted and remodeled floating hydrated gels, providing a biomechanical explanation for the generation of microvessels in vitro. cDNA microarray analysis of highly invasive versus poorly invasive melanoma tumor cells confirmed a genetic reversion to a pluripotent embryonic-like genotype in the highly aggressive melanoma cells. These observations strongly suggest that aggressive melanoma cells may generate vascular channels that facilitate tumor perfusion independent of tumor angiogenesis.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Changing views of the role of matrix metalloproteinases in metastasis.

            Metastatic spread of cancer continues to be the greatest barrier to cancer cure. Understanding the molecular mechanisms of metastasis is crucial for the design and effective use of novel therapeutic strategies to combat metastases. One class of molecules that has been repeatedly implicated in metastasis is the matrix metalloproteinases (MMPs). In this review, we re-examine the evidence that MMPs are associated with metastasis and that they make a functional contribution to the process. Initially, it was believed that the major role of MMPs in metastasis was to facilitate the breakdown of physical barriers to metastasis, thus promoting invasion and entry into and out of blood or lymphatic vessels (intravasation, extravasation). However, recent evidence suggests that MMPs may have a more complex role in metastasis and that they may make important contributions at other steps in the metastatic process. Studies using intravital videomicroscopy, as well as experiments in which levels of MMPs or their inhibitors (tissue inhibitors of metalloproteinases [TIMPs]) are manipulated genetically or pharmacologically, suggest that MMPs are key regulators of growth of tumors, at both primary and metastatic sites. On the basis of this evidence, a new view of the functional role of MMPs in metastasis is presented, which suggests that MMPs are important in creating and maintaining an environment that supports the initiation and maintenance of growth of primary and metastatic tumors. Further clarification of the mechanisms by which MMPs regulate growth of primary and metastatic tumors will be important in the development of novel therapeutic strategies against metastases.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              The morphologic characteristics of tumor blood vessels as a marker of tumor progression in primary human uveal melanoma: a matched case-control study.

              Nine morphologic patterns of tumor vessels were identified in eyes removed for ciliary body or choroidal melanoma by the examination of tissue sections stained with fluorescein-conjugated Ulex europaeus I using laser scanning confocal microscopy. This technique also highlights intravascular tumor invasion. Each of these nine morphologic patterns of tumor vessels also may be demonstrated by a modification of the periodic acid-Schiff reaction, viewed with a green narrow band pass filter, but this modified histochemical technique does not accurately identify intravascular tumor invasion. Most tumors have a heterogeneous distribution of vascular patterns. Melanomas in two groups of 20 tumors each were matched by tumor size and location (one group of tumors from patients who survived at least 15 years free of metastatic melanoma after enucleation and one group of tumors from patients who died of metastatic melanoma). A matched case-control analysis indicates that the presence of at least one closed vascular loop in a uveal melanoma is the most significant vascular pattern associated with death from metastatic melanoma after enucleation. Closed loops are associated with other histologic features that are predictive of an unfavorable outcome after enucleation: epithelioid cells and mitotic figures. In this preliminary study the formation of closed vascular loops is a marker of tumor progression in ciliary body and choroidal melanomas.
                Bookmark

                Author and article information

                Journal
                ORE
                Ophthalmic Res
                10.1159/issn.0030-3747
                Ophthalmic Research
                S. Karger AG
                0030-3747
                1423-0259
                2007
                January 2007
                11 December 2006
                : 39
                : 1
                : 40-44
                Affiliations
                aDepartment of Ophthalmology, Ocular Oncology Service, and bDepartment of Pathology, Hacettepe University School of Medicine, Ankara, Turkey
                Article
                97905 Ophthalmic Res 2007;39:40–44
                10.1159/000097905
                17164576
                © 2007 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 2, Tables: 1, References: 21, Pages: 5
                Categories
                Original Paper

                Comments

                Comment on this article