Current Topics in Pathology 77
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1 Current Topics in Pathology 77 Managing Editors C.L. Berry E. Grundmann Editorial Board H. Cottier, P.I Dawson, H. Denk, C.M. Fenoglio-Preiser Ph.U.Heitz, O.H.Iversen, F.Nogales, N.Sasano, G.Seifert IC.E. Underwood, Y. Watanabe
2 Morphological Tumor Markers General Aspects and Diagnostic Relevance Contributors M. Altmannsberger. R Berndt P. Brandtzaeg 1. Caselitz. T.M. Chu. A.D. Cox I. Damjanov H. Denk Ph. U. Heitz RY. Iozzo. RC. Janzer M. Kiessling P. Kleihues. G. Kloppel. F.R. Korsrud Th. Loning. K. Milde. P. Moller R Moll M. Osborn H.P. Otto T.O. Rognum. K. Schwechheimer P.S. Thrane. G.L. WrightJr. Editor Gerhard Seifert Springer-Verlag Berlin Heidelberg New York London Paris Tokyo
3 G. SEIFERT, Professor Dr., Institut fur Pathologie der Universitiit Hamburg, MartinistraBe 52, UKE, D-2000 Hamburg 20 C.L. BERRY, Professor Dr., Department of Morbid Anatomy, The London, Hospital Medical College, Whitechapel, London E1 tbb, Great Britain E. GRUNDMANN, Professor Dr., Gerhard-Domagk-Institut fur Pathologie der Universitiit, DomagkstraBe 17, D-4400 Munster With 95 Figures, Some in Colour Library of Congress Cataloging-in-Publication Data. Morphological tumor markers. (Current topics in pathology; 77) Includes bibliographies and index. 1. Tumor markers - Diagnostic use. 2. Tumor antigens - Diagnostic use. I. Altmannsberger, M. II. Seifert, Gerhard, III. Series: Current topics in pathology; v.77. [DNLM; 1. Antigens, Neoplasm - analysis. 2. Histocytochemistry. 3. Immunochemistry. 4. Immunologic Technics. 5. Neoplasms - diagnosis. 6. Receptors, Endogenous Substances. WI CU821H v.77/qz 241 M871] RB1.E6 vol s [RC270.3.T84] [616.99'207'58] ISBN-13: e-isbn-13: DOl: / This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in other ways, and storage in data banks. Duplication of this publication or parts thereof is only permitted under the provisions of the German Copyright Law of September 9, 1965, in its version of June 24, 1985, and a copyright fee must always be paid. Violations fall under the prosecution act of the German Copyright Law. Springer-Verlag Berlin Heidelberg 1987 Softcover reprint of the hardcover I st edition 1987 The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product Liability: The publishers can give no guarantee for information about drug dosage and application thereof contained in this book. In every individual case the respective user must check its accuracy by consulting other pharmaceutical literature. 2122/
4 List of Contributors ALTMANNSBERGER, M., BERNDT, R., Dr. BRANDTZAEG, P., CASELITZ, J., Dr. CHU, T.M., Cox, A.D., Dr. DAMJANOV, I., DENK,H., Univ.- HEITZ, Ph.U., Institut fur Pathologie, Klinikum der Justus-Liebig-Universitat GieBen, LanghansstraBe 10, D-6300 GieBen Institut fur Allgemeine Pathologie und pathologische Anatomie der Universitat, 1m Neuenheimer Feld , D-6900 Heidelberg Laboratory for Immunohistochemistry and Immunopathology, Rikshospitalet, N Oslo 1 Institut fur Pathologie der Universitat Hamburg, MartinistraBe 52, UKE, D-2000 Hamburg 20 Diagnostic Immunology Research and Biochemistry Department, Roswell Park Memorial Institute, Buffalo, NY 14263, USA Department of Microbiology and Immunology, Eastern Virginia Medical School, PO Box 1980, Norfolk, VA 23501, USA Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA Institut fur Pathologische Anatomie der Universitat, Auenbruggerplatz 25, A-8036 Graz Institut fur Pathologie der Universitat, Sch6nbeinstraBe 40, CH-4003 Basel
5 VI lozzo, R.V., Dr. JANZER, R.C., Dr. KIESSLING, M., Dr. KLEIHUES, P., KLOPPEL, G., KORSRUD, F.R., Dr. WNING, TH., MILDE, K., Dr. List of Contributors Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 3400 Spruce Street G/1, Philadelphia, PA USA Abteilung Neuropathologie, Institut fur Pathologie, Universitat Zurich, CH-8091 Zurich Abteilung Neuropathologie, Pathologisches Institut, Universitat Freiburg, D-7800 Freiburg Abteilung Neuropathologie, Institut fur Pathologie, Universitat Zurich, CH-8091 Zurich Institut fur Pathologie der Universitat Hamburg, MartinistraBe 52, UKE, D-2000 Hamburg 20 Laboratory for Immunohistochemistry and Immunopathology, Rikshospitalet, N-0027 Oslo 1 Institut fur Pathologie der Universitiit Hamburg, MartinistraBe 52, UKE, D-2000 Hamburg 20 Institut fur Pathologie der Universitat Hamburg, MartinistraBe 52, UKE, D-2000 Hamburg 20 MOLLER, P., Dr. MOLL, R., Dr. OSBORN, MARY, Dr. Institut fur Allgemeine Pathologie und pathologische Anatomie der Universitat, 1m Neuenheimer Feld , D-6900 Heidelberg Institut fur Pathologie, Klinikum der Johannes Gutenberg-Universitat, LangenbeckstraBe 1, D-6500 Mainz Max-Planck-Institut fur biophysikalische Chemie, Am Fassberg, D-3400 Gottingen
6 List of Contributors VII OTTO, H.F., ROGNUM, T.O., Dr. SCHWECHHEIMER, K., Dr. THRANE, P.S., Dr. WRIGHT Jr., G.L., Institut fur Allgemeine Pathologie und pathologische Anatomie der Universitiit, 1m Neuenheimer Feld , D-6900 Heidelberg Institute of Forensic Medicine and Laboratory for Immunohistochemistry and Immunopathology, Institute of Pathology, Rikshospitalet, N-0027 Oslo 1 Institut fur Allgemeine Pathologie und pathologische Anatomie der Universitiit, 1m Neuenheimer Feld , D-6900 Heidelberg Laboratory for Immunohistochemistry and Immunopathology, Institute of Pathology, Rikshospitalet, N-0027 Oslo 1, and Department of Oral Surgery and Oral Medicine, Dental Faculty, University of Oslo, Geitemyrsveien 71, N-0455 Oslo 1 Department of Microbiology and Immunology, Eastern Virginia Medical School, PO Box 1980, Norfolk, VA 23501, USA
7 Preface New methods open new insights and provide the basis for new concepts in cancer reseach. The discovery of monoclonal antibodies and the further development of immunocytochemistry and hybridization techniques has led to a "renaissance" of pathology in the field of tumor classification and prognosis as well as in oncotherapy. The application of the new marker methods may result in a more intensive integration of morphological findings into clinical practice. In recent years an increasing battery of commercially available antibodies has made a progressively more detailed classification of tumors possible using a broader spectrum of immunocytochemical methods. All scientific journals publish papers about the results of these new applications in tumor diagnosis. Principally, we must differentiate between biological and morphological tumor markers. In this monograph the importance of morphological tumor markers is the focus of the presentation by an international group. As an introduction, two chapters offer accounts of the application of monoclonal antibodies to human tumor antigens and the important role of biochemical markers in human cancer. A special chapter refers to the different immunocytochemical methods for the demonstration of tumor markers and their relevance in diagnostic pathology. The so-called tumor markers are very often cell or tissue markers which provide data related to the problems of cytogenesis, cell function or cell differentiation. In contrast with the evidence from biological markers, the methods of immunocytochemistry or hybridization techniques permit the demonstration of tumor markers precisely, on the cell membrane, in the organelles of the cytoplasm or in the nucleus. In the very heterogeneous group of morphological tumor markers the intermediate filaments of the cytoskeleton, glycoconjugate antigens of the cell membrane and special proteins such as enzymes play the major role in routine diagnostic work. From the histogenetic point of view, markers of different tissues can be distinguished. This fact is the organizing principle of the majority of chapters. The epithelial tumor markers include widely varying substances (cytokeratins, tissue polypeptide antigen, epithelial membrane antigen, oncofetal antigens, markers of glandular differentiation). Mesenchymal markers consist of some intermediate filaments (e.g. vimentin, desmin etc.), special proteins and enzymes. Other markers are
8 x Preface suitable for demonstration of the intercellular matrix (proteoglycans, basal membrane antigens), blood group substances, lectins or neuroendocrine products. Further chapters demonstrate the importance of tumor markers in neuro-oncology and viral-associated tumors. The conclusion of the monograph is an overview on the theme of "cell, tissue and organ specific tumor markers". Altogether the monograph is a review of methods and practical application of the different morphological tumor markers in the field of tumor diagnosis and prognosis. Organ specific diagnosis has a very great clinical relevance for treatment and prognosis. Therefore, this volume brings all pathologists and oncologically orientated clinicians up to the state of the art in cancer detection and diagnosis. I would like to thank very much all contributors for their excellent cooperation in timing and arrangement of the chapters. I am also grateful for the outstanding work on this volume by Springer-Verlag, in particular Mrs. H. Herion and Mrs. U.S. Davis. Hamburg G. SEIFERT
9 Contents Monoclonal Antibodies to Human Tumor Antigens G.L. WRIGHT Jr. and A.D. Cox... Biochemical Markers for Human Cancer T.M. CHU Immunohistochemical Methods for the Demonstration of Tumor Markers With 7 Figures H. DENK Epithelial Tumor Markers: Cytokeratins and Tissue Polypeptide Antigen (TPA) With 5 Figures R. MOLL Epithelial Tumor Markers: Oncofetal Antigens (Carcinoembryonic Antigen, Alpha Fetoprotein) and Epithelial Membrane Antigen With 13 Figures G. KU)PPEL and J. CASELITZ Epithelial Tumor Markers: Special Markers of Glandular Differentiation With 6 Figures T.O. ROGNUM, P.S. THRANE, F.R. KORSRUD and P.BRANDTZAEG Mesenchymal Tumor Markers: Intermediate Filaments With 8 Figures W. ALTMANNSBERGER and M. OSBORN Mesenchymal Tumor Markers: Special Proteins and Enzymes With 6 Figures H.F.OTTo, R.BERNDT, K.SCHWECHHEIMER and P.MoLLER.. 179
10 XII Contents Proteoglycans and the Intercellular Tumor Matrix With 4 Figures R.V.Iozzo Basal Membrane Antigens as Tumor Markers With 7 Figures J. CASELITZ Lectins and Blood Group Substances as "Tumor Markers" With 7 Figures J. CASELITZ Neuroendocrine Tumor Markers With 12 Figures PH.D. HEITZ Morphological Markers in Neuro-Oncology With 2 Figures P. KLEIHUES, M. KIESSLING and R.C. JANZER Viral Tumor Markers With 16 Figures TH. LONING and K. MILDE Cell, Tissue and Organ Specific Tumor Markers: An Overview With 2 Figures I. DAMJANOV 367 Subject Index 385 Indexed in ISR
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