Distinct expression patterns of the immunogenic differentiation antigen NY-BR-1 in normal breast, testis and their malignant counterparts.

Abstract

NY-BR-1 is a differentiation antigen and a potential target for cancer immunotherapy. Its mRNA expression is restricted to breast, testis, prostate and breast cancer by RT-PCR. In this study, we correlated NY-BR-1 protein and mRNA expression on tissue microarrays of mammary, prostatic and testicular malignancies using immunohistochemistry and in situ hybridization with probes for exon 4-7 and 30-33. NY-BR-1 mRNA was confined to primary spermatocytes, suggesting a role in spermatogenesis. Exon 4-7 and 30-33 were equally expressed this cell type. However, NY-BR-1 was absent in all germ cell tumours analyzed (n = 475) and present in one of 56 (2%) prostate carcinomas. In breast, NY-BR-1 mRNA expression was detected in 307 of 442 (70%) primary carcinomas, with strong correlation to its protein expression (p < 0.0001). mRNA expression was significantly stronger and more frequently detected by the exon 30-33 probe than by the exon 4-7 probe (70% vs. 35%, p < 0.0001), indicating the presence of alternative splice variants that lack 5-prime sequences. A similar restricted mRNA pattern was also observed in the normal breast epithelium. NY-BR-1 protein and mRNA correlated significantly with estrogen receptor alpha (ER alpha) protein expression (p < 0.0001), with stronger association to NY-BR-1 mRNA than protein (odds ratio 7.7 compared to 4.6). We identified 4 estrogen response elements (ERE)-like sequences nearby the promoter region, suggesting that NY-BR-1 transcription might be controlled by ER alpha. Accordingly, analysis of matching pairs of primary tumors with their recurrences showed a marked decrease of NY-BR-1 expression in recurrences after tamoxifen treatment (p < 0.0001).

• Authors: Jean-Philippe Theurillat, Ursina Zürrer-Härdi, Zsuzsanna Varga, André Barghorn, Elisabeth Saller, Claudia Frei, Martina Storz, Silvia Behnke, Burkhardt Seifert, Mathias Fehr, Daniel Fink, Christoph Rageth, Claudia Linsenmeier, Bernhard Pestalozzi, Yao-Tseng Chen, Alexander Knuth, Dirk Jäger, Holger Moch
• Journal: International journal of cancer (Int J Cancer) Vol. 122 Issue 7 Pg. 1585-91 (Apr 01 2008) ISSN: 1097-0215 [Electronic] United States
• PMID: 18041742 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2007 Wiley-Liss, Inc.

Chemical References

• ANKRD30A protein, human
• Antigens, Neoplasm
• Antineoplastic Agents, Hormonal
• Biomarkers, Tumor
• Estrogen Receptor Modulators
• RNA, Messenger
• Receptors, Estrogen
• Tamoxifen

Topics

• Antigens, Neoplasm (analysis, genetics)
• Antineoplastic Agents, Hormonal (therapeutic use)
• Biomarkers, Tumor (analysis)
• Breast (immunology)
• Breast Neoplasms (immunology)
• Estrogen Receptor Modulators (therapeutic use)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• In Situ Hybridization
• Male
• Prostatic Neoplasms (immunology)
• RNA, Messenger (analysis)
• Receptors, Estrogen (metabolism)
• Response Elements
• Tamoxifen (therapeutic use)
• Testicular Neoplasms (immunology)
• Testis (immunology)