Expression of MAGE antigens and analysis of the inflammatory T-cell infiltrate in human seminoma |
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| Authors: | Rainer Grobholz Caroline S Verbeke Christiane Schleger Kai-Uwe Köhrmann Beatrix Hein Georg Wolf Uwe Bleyl Giulio C Spagnoli Keren Coplan Denise Kolb Kristin Iversen Achim A Jungbluth |
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| Institution: | (1) Department of Pathology, Ruprecht-Karls University Heidelberg, University Hospital Mannheim, Theodor-Kutzer-Ufer 1–3, 68167 Mannheim, Germany e-mail: rainer.grobholz@path.ma.uni-heidelberg.de Tel.: +49-621-383-3505; Fax: +49-621-383-2005, DE;(2) Department of Urology, Ruprecht-Karls University Heidelberg, University Hospital Mannheim, Theodor-Kutzer-Ufer 1–3, 68167 Mannheim, Germany, DE;(3) Department of Surgery and Research, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland, CH;(4) Ludwig Institute for Cancer Research at Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA, US |
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| Abstract: | The MAGE gene family encodes antigens that are recognized by cytotoxic T-cells. The expression of MAGE antigens has been
linked to tumor stage, and MAGE peptides are under investigation as possible vaccines. Seminomas are tumors that are typically
accompanied by a heavy inflammatory infiltrate, but have not been studied with regard to their MAGE antigen expression and
its correlation with the inflammatory infiltrate. We investigated, therefore, MAGE protein expression, the amount of cytotoxic
T-cells, clonality of the lymphocytic infiltrate, apoptotic activity and occurrence of necrosis. Specimens of 27 patients
with classical seminoma were examined by immunohistochemistry for CD4, CD8, CD56, CD45R0, β2-microglobulin and HLA-DR. MAGE expression was detected with the monoclonal antibody 57B, reactive with MAGE-1, -3, -4, -6
and -12. Clonality of the inflammatory infiltrate was examined by multiplex polymerase chain reaction (PCR) analysis of the
T-cell receptor rearrangement. Apoptotic cells were detected by DNA nick-end labeling of fragmented DNA, and the apoptotic
index was determined semi-quantitatively. Expression of 57B was found in 19 (70%) of 27 seminomas. In all cases, more than
70% of T-cells expressed CD45R0. In four cases, a predominant infiltration of CD8-positive cytotoxic T-cells (CD4/CD8 ratio <1)
was present. However, 15 seminomas showed a CD4/CD8 ratio >1. In all cases, infiltration of CD56-positive natural killer cells
was only focal. HLA-DR expression was not detectable in tumor tissue; β2-microglobulin was only focal in three cases. Analysis of the T-cell clonality revealed a polyclonal population. The apoptotic
index was not significantly different in 57B-positive seminomas (4.15%) compared with 57B negative seminomas (3.80%). Also,
no correlation between the 57B expression and the occurrence of necrosis was found. MAGE antigens are homogeneously expressed
in most seminomas, but their presence does not appear to represent a dominant epitope responsible for the lymphocytic infiltrate.
Received: 11 April 2000 / Accepted: 1 August 2000 |
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| Keywords: | MAGE Seminoma Tumor-infiltrating lymphocytes |
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