Recent Results in Cancer Research 139

Managing Editors Ch. Herfarth, Heidelberg. H.-f. Senn, St. Gallen

Associate Editors M. Baum, London· V. Diehl, K6ln F. Gutzwiller, Zurich· M. F. Rajewsky, Essen M. Wannenmacher, Heidelberg

Founding Editor P. Rentchnik, Geneva

c. Garbe S. Schmitz C.E. Orfanos (Eds.)

Skin Cancer: Basic Science, Clinical Research and Treatment

With 85 Figures and 72 Tables

Springer-Verlag Berlin Heidelberg New York London Paris Tokyo Hong Kong Barcelona Budapest

Prof. Dr. med. Claus Garbe Dr. med. Stefan Schmitz Prof. Dr. med. Prof. h.c. Constantin E. Orfanos

Freie Universitat Berlin University Department of Dermatology Medical Centre Benjamin Franklin Hindenburgdamm 30 12200 Berlin, Germany

ISBN-13: 978-3-642-78773-7 DOl: 10.1007/978-3-642-78771-3

e-ISBN-13: 978-3-642-78771-3

Library of Congress Cataloging-in-Publication Data. Skin Cancer: basic science, clini­cal research, and treatmentiC Garbe, S. Schmitz. CE. Orfanos (eds.). p. cm.­(Recent results in cancer research; 139) Includes bibliographical references and index.

Cancer - Congresses. I. Garbe, C (Claus), 1951- . II. Schmitz, S. (Stefan), 1960- . III. Orfanos, CE. (Constantin E.) IV. Series. [DNLM: 1. Skin Neoplasms - congresses. WI RE106P v. 139 1995] RC26l.R35 vol. 139 [RC280.S5] 616.99'4 s - dc20 [616.99'477] DNLMIDLC for Library of Congress 94-36423

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Preface

In the past two decades, considerable interest in skin cancer has developed in the public and scientific communities. There may have been several reasons for this:

- The rise in the global incidence of cutaneous cancers - New molecular biology techniques resulting in a better

understanding of pathogenesis and improved diagnostic procedures

- The advent of new pathological entities, e.g., the endemic form of Kaposi's sarcoma

- A constantly increasing range of therapeutic modalities, providing even more efficacious treatment and manage­ment of skin cancers

As N.E. Fusenig describes in the first chapter of this volume, basic research is only beginning to unravel the complex mechanism involved in cellular dedifferentiation and tumor progression. Progress is dearly needed, especially in dermato­oncology, where the rise in the incidence of epithelial tumors has inflated the overall skin cancer incidence. The incidence of tumors of the skin exceeds that of all other neoplasias in humans, with recreational sun exposure being a suspected primary cause. Several studies on the effects of UV radiation have been included at the beginning of this volume. Even the role of long wavelength UV (UVA) has become a focus of research activities. The main concern is that the low carcinogenicity of UVA, in comparison to UVB, may be outweighed and exceeded in its effects by increased UV A exposure, e.g., in tanning parlors, and possibly also by using UVB sunscreens, thus prolonging the time for UV erythema to develop. Interestingly, the recent increase in

VI Preface

epithelial skin cancers is not confined exclusively to whites, but rather it is a global phenomenon, as indicated by the Japanese data presented.

A marked increase in incidence has been recorded for malignant melanoma in the past four decades. Melanoma research attracted most of the attention during the con­ference as melanoma is the tumor with the highest mortality of all skin tumors. Basic molecular research and studies on the properties of metastasizing melanoma cells were key issues, as reflected by the respective selection of articles. In addition, some promising approaches in immunotargeting and cytokine research were included. The interaction of melanoma cells with immunocompetent cells and the role of cellular surface molecules were further topics. The increased incidence of melanoma has coincided with in­creased publicity, which raised such issues as prevention and early diagnosis, represented in this volume in particular by US studies.

The research on cutaneous lymphomas has been do­minated by developments in molecular biology, mainly resulting in refined diagnostic procedures. Today northern blotting and polymerase chain reaction have become major supplements to routine immunohistochemical techniques. The application of the newer techniques goes beyond the study of T-cell lymphomas, as described in one article, where oncogenes in B-celllymphomas have been analyzed.

Much attention has been devoted to HIV-associated Kaposi's sarcoma by the medical community and the public during the past decade. A large follow-up study of Kaposi patients is presented which comprises over 10 years of therapeutic experience in Berlin, Germany. A detailed dis­cussion of various etiologic theories is included. A report of the clinical research on basal cell carcinomas and adnexal tumors concludes the tumor section.

The last part of the volume contains articles dealing with treatment and management of skin tumors, again, malignant melanoma being the main focus of interest. Current debates on melanoma treatment are covered in detail, i.e., excisional margins, elective lymphadenectomy, systemic treatment. The scope of the therapeutic approaches ranges from vaccination therapy, and the use of cytokines to the combination of the latter with chemotherapeutic agents, with reference to the state of the art in the treatment of T-cell lymphomas and the Kaposi's sarcoma. Two relatively new therapeutic modalities are the application of extracorporeal photo-

Preface VII

pheresis for treatment of T-cell lymphomas and the appli­cation of lasers, especially for photodynamic therapy. The therapeutic section of the volume thus provides a concise review of treatment of skin cancer.

Overall a selection of articles is presented which repre­sent the major scientific and clinical debates being con­ducted in the field. We hope that this volume will prove useful to all readers interested in skin oncology.

Berlin, November 1994 The Editors

Contents

I. Carcinogenesis ......... . . . . . . . . .

N.E. Fusenig, D. Breitkreutz, P. Boukamp, P. Tomakidi, and H. -f. Stark

1

Differentiation and Tumor Progression . . . . . . . . . . 1

F.R. de Gruijl Action Spectrum for Photocarcinogenesis . . . . . . . .. 21

T.M. Runger, B. Epe, and K. Moller Processing of Directly and Indirectly Ultraviolet-Induced DNA Damage in Human CeIIs . . . . . . . . .. 31

S. Schmitz, C. Garbe, K. fimbow, A. Wulff, H. Daniels, f. Eberle, and C.E. Orfanos Photodynamic Action of Ultraviolet A: Induction of CeIIular Hydroperoxides . . . . . . . . . .. 43

A. van Elsas, S. Zerp, S. van der Flier, M. Kruse-Wolters, A. Vacca, D.J. Ruiter, and P. Schrier Analysis of N-ras Mutations in Human Cutaneous Melanoma: Tumor Heterogeneity Detected by Polymerase Chain Reaction/Single-Stranded Conformation Polymorphism Analysis . . . . . . . 57

l.M. Leigh and M. T. Glover Skin Cancer and Warts in Immunosuppressed Renal Transplant Recipients 69

X Contents

l. Slade, T. G. Salopek, A.A. Marghoob, A. W. Kopf, and D.S. Rigel Risk of Developing Cutaneous Malignant Melnoma in Atypical-Mole Syndrome: New York University Experience and Literature Review . . . . . . . . . . . .. 87

II. Malignant Melanoma. . . . . . . . . . . . . . . . . . .. 105

G.N.P. van Muijen, E.H.l. Danen, T.l. de Vries, P.H.A. Quax, l.H. Verheijen, and D.l. Ruiter Properties of Metastasizing and Nonmetastasizing Human Melanoma Cells . . . . . . . . . . . . . . . . . . .. 105

l. Eberle, C. Garbe, G. Kroumpouzos, and c.E. Orfanos Protein Patterns of Benign and Malignant Human Melanocytes Show Consistent Changes in Gene Expression . . . . . . . . . . . . . . . . . . . . . .. 123

l. Weiss, M. Heine, K.c. Arden, B. Korner, H. Pilch, R.A. Herbst, and E. G. lung Mutation and Expression of TP53 in Malignant Melanomas. . . . . . . . . . . . . . . . . . .. 137

S. Kriiger-Krasagakes, K. Krasagakis, C. Garbe, and T. Diamantstein Production of Cytokines by Human Melanoma Cells and Melanocytes . . . . . . . . . . . . . . . . . . . . . . . .. 155

K. Krasagakis, C. Garbe, Ch. C. Zouboulis, and C. E. Orfanos Growth Control of Melanoma Cells and Melanocytes by Cytokines . . . . . . . . . . . . . . . . . . . . . . . . . .. 169

D. Schadendorf, M. Worm, K. lurgovsky, E. Dippel, U. Reichert, and B.M. Czarnetzki Effects of Various Synthetic Retinoids on Proliferation and Immunophenotype of Human Melanoma Cells In Vitro ............ 183

T. Vogt, W. Stolz, U. Hohenleutner, R. Schiffner, and M. Landthaler Prognostic Significance of DNA Cytometry in Comparison with Histologic Measurements in Malignant Melanomas. . . . . . . . . . . . . . . . . . .. 195

Contents XI

J.C Becker and E.B. Brocker Lymphocyte-Melanoma Interaction: Role of Surface Molecules. . . . . . . . . . . . . . . . . .. 205

H. K. Koh and A. C Geller Melanoma Control in the United States: Current Status .. . . . . . . . . . . . . . . . . . . . . . . .. 215

III. Cutaneous Lymphoma . . . . . . . . . . . . . . . . .. 225

G. Burg, A. Haffner, R. Bani, S. Dommann, and R. Dummer New Perspectives in Experimental and Clinical Research for Cutaneous T Cell Lymphomas. . . . . .. 225

G. Staib and W. Sterry Use of Polymerase Chain Reaction in the Detection of Clones in Lymphoproliferative Diseases of the Skin

S.A. Garatti, E. Roscetti, D. Trecca, N.S. Fracchiolla, A. Neri, and E. Berti bel-I, bel-2, p53, c-myc, and lyt-lO Analysis

239

in Cutaneous Lymphomas ................... 249

IV. Other Skin Cancers . . . . . . . . . . . . . . . . . . .. 263

M. Ichihashi, K. Naruse, S. Harada, T. Nagano, T. Nakamura, T. Suzuki, N. Wadabayashi, and S. Watanabe Trends in Nonmelanoma Skin Cancer in Japan 263

C£. Orfanos, R. Husak, U. Wolfer, and C Garbe Kaposi's Sarcoma: A Reevaluation. . . . . . . . . . 275

R. Rompel, J. Petres, K. Kaupert, and G. Muller-Eckhardt Human Leukocyte Antigens and Multiple Basal Cell Carcinomas 297

U. Wollina, E. Castelli, and D. Rulke Immunohistochemistry of Eccrine Poroma and Porocarcinoma - More Than Acrosyringeal Tumors? . 303

XII Contents

v. Treatment and Management . . . . . . . . . . . . . .. 317

N. Cascinelli and M. Santinami Excision of Primary Melanoma Should Allow Primary Closure of the Wound

R. Rompel, C. Garbe, P. Biittner, K. Teichelmann, and 1. Petres Role of Elective Lymph Node Dissection in Stage I Malignant Melanoma:

317

Evaluation by Matched Pair Analysis. . . . . . .. 323

1. -co Bystryn Clinical Activity of a Polyvalent Melanoma Antigen Vaccine . . . . . . . . . . . . . . . . . . . . . . . .. 337

C. Garbe Perspectives of Cytokine Treatment in Malignant Skin Tumors . . . . . . . . . . . . . . . . . .. 349

E.D. Kreuser, S. Wadler, and E. Thiel Biochemical Modulation of Cytotoxic Drugs by Cytokines: Molecular Mechanisms in Experimental Oncology . .. 371

U. Keilholz, C. Scheibenbogen, P. Brossart, T. Mohler, W. Tilgen, and W. Hunstein Interleukin-2-Based Immunotherapy and Chemoimmunotherapy in Metastatic Melanoma.. 383

R. Stadler and H. G. Otte Combination Therapy of Cutaneous T Cell Lymphoma with Interferon Alpha-2a and Photochemotherapy . .. 391

v. Mielke, G. Staib, and W. Sterry Systemic Treatment for Cutaneous Lymphomas. . . .. 403

H.P.M. Gollnick, M. Owsianowski,l. Ramaker, S. C. Chun, and C. E. Orfanos Extracorporeal Photopheresis - A New Approach for the Treatment of Cutaneous T Cell Lymphomas 409

M. Landthaler, R.-M. Szeimies, and U. Hohenleutner Laser Therapy of Skin Tumors . . . . . . . . . . . . . . .. 417

Contents XIII

M.A. Conant Management of Human Immunodeficiency Virus-Associated Malignancies. . . . . . . . . . . . . . .. 423

SUbject Index . . . . . . . . . . . . . . . . . . . . . . . . . .. 433

List of Contributors*

Arden, K.C. 1371

Becker, J.C. 205 Berti, E. 249 Boni, R. 225 Boukamp, P. 1 Breitkreutz, D. 1 Brocker, E.B. 205 Brossart, P. 383 Burg, G. 225 Buttner, P. 323 Bystryn, J.-C. 337 Cascinelli, N. 317 Castelli, E. 303 Chun, S.C. 409 Conant, M.A. 423 Czarnetzki, B.M. 183 Danen, E.H.J. 105 Daniels, H. 43 de Gruijl, F.R. 21 de Vries, T.J. 105 Diamantstein, T. 155 Dippel, E. 183 Dommann, S. 225 Dummer, R. 225 Eberle, J. 43, 123 Epe, B. 31

Fracchiolla, N.S. 249 Fusenig, N .E. 1 Garatti, S.A. 249 Garbe, C. 43, 123, 155,

169, 275, 323, 349 Geller, A.C. 215 Glover, M.T. 69 Gollnick, H.P .M. 409 Haffner, A. 225 Harada, S. 263 Heine, M. 137 Herbst, R.A. 137 Hohenleutner, U. 195,417 Hunstein, W. 383 Husak, R. 275 Ichihashi, M. 263 Jimbow, K. 43 Jung, E.G. 137 Jurgovsky, K. 183 Kaupert, K. 297 Keilholz, U. 383 Koh, H.K. 215 Kopf, A.W. 87 Korner, B. 137 Krasagakis, K. 155,169 Kreuser, E.D. 371

* The address of the principal author is given on the first page of each contribution. 1 Page on which contribution begins.

XVI List of Contributors

Kroumpouzos, G. 123 Kriiger-Krasagakes, S. 155 Kruse-Wolters, M. 57 Landthaler, M. 195, 417 Leigh, I.M. 69 Marghoob, AA 87 Mielke, V. 403 Mohler, T. 383 Moller,K. 31 Muller-Eckhardt, G. 297 Nagano, T. 263 Nakamura, T. 263 Naruse, K. 263 Neri, A 249 Orfanos, C.E. 43, 123,

169, 275, 409 Otte, H.G. 391 Owsianowski, M. 409 Petres, J. 297,323 Pilch, H. 137 Quax, P.H.A. 105 Ramaker, J. 409 Reichert, U. 183 Rigel, D.S. 87 Rompel, R. 297, 323 Roscetti, E. 249 Ruiter, D.J. 57, 105 Riilke, D. 303 Runger, T.M. 31 Salopek, T.G. 87 Santinami, M. 317 Schadendorf, D. 183 Scheibenbogen, C. 383

Schiffner, R. 195 Schmitz, S. 43 Schrier, P. 57 Slade, J. 87 Stadler, R. 391 Staib, G. 239, 403 Stark, H.-J. 1 Sterry, W. 239, 403 Stolz, W. 195 Suzuki, T. 263 Szeimies, R.-M. 417 Teichelmann, K. 323 Thiel, E. 371 Tilgen, W. 383 Tomakidi, P. 1 Trecca, D. 249 Vacca, A. 57 van der Flier, S. 57 van Elsas, A. 57 van Muijen, G.N.P. 105 Verheijen, J.H. 105 Vogt, T. 195 Wadabayashi, N. 263 Wadler, S. 371 Watanabe, S. 263 Weiss, J. 137 Wolfer, U. 275 Wollina, U. 303 Worm, M. 183 Wulff, A. 43 Zerp, S. 57 Zouboulis, Ch.C. 169