Detection of MAGE-4 protein in sera of patients with head-and-neck squamous-cell carcinoma

Abstract

The MAGE-4 gene, a member of the MAGE gene family, is expressed in various cancers, including head-and-neck squamous-cell carcinomas (HN-SCC), but is not expressed in any normal tissues except for the testis and placenta. The aim of this study was to determine whether serum MAGE-4 protein is a useful tumor marker for detection of HN-SCC. An enzyme-linked immunosorbent assay was used to measure serum level of MAGE-4 protein. The serum level of MAGE-4 in pre-operative HN-SCC patients was significantly higher than that in patients with non-malignant diseases (NMD) of the head and neck, volunteers undergoing cancer screening (VOL), or healthy donors (HD). When the cut-off level was determined at 1.15 ng/ml (mean plus 3 SD of HD), sera from 28 of 96 patients with HN-SCC (p F 0.0001 vs. the other groups), 7 of 82 patients with NMD, 2 of 92 with VOL, and 0 of 68 HD were positive for MAGE-4. Serum levels of MAGE-4 protein in all 7 HN-SCC patients whose sera were positive for MAGE-4 before operation decreased after operation, and, in one patient, a renewed rise in serum level was followed by recurrence. These results indicate that MAGE-4 protein is detectable in sera of a significant number of HN-SCC patients, and that serum MAGE-4 protein might be a useful tumor marker to monitor the recurrence of MAGE-4-positive HN-SCC. Int. J. Cancer, 70:287-290, 1997.r 1997 Wiley-Liss, Inc.The MAGE gene family consists of at least 12 closely related genes located on the long arm of chromosome X ( Van der Bruggen et al., 1991;Traversari et al., 1992;Gaugler et al., 1994;De Plaen et al., 1994). Among them, the MAGE-1 or -3 gene codes for tumor antigens on HLA-A1 and -Cw1601 or -A1 and -A2 recognized by cytotoxic T lymphocytes Van der Bruggen et al., 1994a,b). genes are preferentially expressed at the mRNA level in many different cancers, including head-and-neck squamous-cell carcinoma (HN-SCC) (Van der Bruggen et al., 1991; 1994a,b;Traversari et al., 1992;Gaugler et al., 1994;De Plaen et al., 1994;Weynants et al., 1994; Shichijo et al., 1995a,b;Eura et al., 1995). In contrast, no normal cells other than testis and placenta express the MAGE genes (Weynants et al., 1994;Takahashi et al., 1995). We have developed an enzymelinked immunosorbent assay (ELISA) for detection of MAGE-4 protein (Shichijo et al., 1995a,b). The present study addresses the question of whether serum MAGE-4 protein is a useful tumor marker for detection of HN-SCC. MATERIAL AND METHODS Sample collectionPeripheral blood was obtained from 96 pre-operative HN-SCC patients, and 82 patients with non-malignant diseases (NMD) of the head and neck (dental caries, periodontal disease, fracture, cyst, benign tumor, odontogenic infection, sinusitis, tonsillitis and pharyngitis) on their initial visit to the out-patients' clinic of the Department of Oral Surgery of the Kurume University School of Medicine, or the Department of Otolaryngology of Kumamoto University School of Medicine. The control sera were obtained from 68 healthy donors (HD). The mean age of the HD was much l...

Biological and clinical relevance of transcriptionally active human papillomavirus (HPV) infection in oropharynx squamous cell carcinoma

“…Similarly, the expression of MAGEA4 , MAGEA12 , and the HMGA2 oncogene are markedly decreased. They are known to be overexpressed in oral carcinoma,36–38 and may therefore only appear to be down‐regulated in HPV‐positive lesions, since the comparison is with HPV‐negative HNSCC. We found that the expression of the CCNA1 ( cyclin A ) gene is diminished in RNA‐positive samples.…”

Prognostic value of intratumoral CD8+ T lymphocyte in extrahepatic bile duct carcinoma as essential immune response

“…(2) cancer-testes antigens (CTAs) expressed in the testes and a variety of malignancies; and (3) tumor-specific antigens that arise from mutations in tumor cells [14][15][16][17][18][19][20][21]. When a cell expresses a protein that is not produced in normal tissues, fragments of them are put onto the HLA molecules and the cell is recognized as a ''nonself'' by CD8 þ T-lymphocytes.…”

A MAGE-A4 peptide presented by HLA-A2 is recognized by cytolytic T lymphocytes

“…Different modes of immunization can be envisaged: a synthetic peptide, DC pulsed with this peptide, a MAGE-A4 protein, or viral vectors encoding the epitope. In clinical trials, the availability of monoclonal and polyclonal anti-MAGE-A4 antibodies may facilitate the detection of the MAGE-A4 protein, both in tissue sections and in the serum of cancer patients [34,35].…”