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

Int J Cancer. 2008 Apr 1;122(7):1585-91. doi: 10.1002/ijc.23241.

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).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / analysis*
  • Antigens, Neoplasm / 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*

Substances

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