Expression of MAGE antigens and analysis of the inflammatory T-cell infiltrate in human seminoma Journal Article


Authors: Grobholz, R.; Verbeke, C. S.; Schleger, C.; Köhrmann, K. U.; Hein, B.; Wolf, G.; Bleyl, U.; Spagnoli, G. C.; Coplan, K.; Kolb, D.; Iversen, K.; Jungbluth, A. A.
Article Title: Expression of MAGE antigens and analysis of the inflammatory T-cell infiltrate in human seminoma
Abstract: 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 de-termined 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.
Keywords: immunohistochemistry; adult; clinical article; controlled study; human tissue; protein expression; middle aged; unclassified drug; cancer staging; polymerase chain reaction; cd8 antigen; antigen expression; t lymphocyte; lymphocytes, tumor-infiltrating; t-lymphocytes; apoptosis; cell infiltration; neoplasm proteins; inflammation; gene product; cytotoxicity; necrosis; monoclonal antibody; t lymphocyte receptor; antibodies, monoclonal; dna; antigens, neoplasm; melanoma antigen 1; melanoma antigen 3; hla dr antigen; cytotoxic t lymphocyte; testicular neoplasms; natural killer cell; antibody specificity; beta 2 microglobulin; cd4 antigen; lymphocytic infiltration; nick end labeling; seminoma; cd45 antigen; melanoma antigen 4; dna fragment; tumor-infiltrating lymphocytes; mage; receptors, antigen, t-cell, gamma-delta; tumor necrosis; in situ nick-end labeling; cd56 antigen; polyclonal activation; humans; human; male; priority journal; article; protein mage; protein mage 12; protein mage 6
Journal Title: Urological Research
Volume: 28
Issue: 6
ISSN: 0300-5623
Publisher: Springer  
Date Published: 2000-12-01
Start Page: 398
End Page: 403
Language: English
DOI: 10.1007/s002400000143
PUBMED: 11221919
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 18 November 2015 -- Source: Scopus
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MSK Authors
  1. Achim Jungbluth
    454 Jungbluth
  2. Denise Frosina
    123 Frosina
  3. Keren Anne Coplan
    42 Coplan
  4. Kristin A Iversen
    58 Iversen