Premium
Distinct expression patterns of the immunogenic differentiation antigen NY‐BR‐1 in normal breast, testis and their malignant counterparts
Author(s) -
Theurillat JeanPhilippe,
ZürrerHärdi Ursina,
Varga Zsuzsanna,
Barghorn André,
Saller Elisabeth,
Frei Claudia,
Storz Martina,
Behnke Silvia,
Seifert Burkhardt,
Fehr Mathias,
Fink Daniel,
Rageth Christoph,
Linsenmeier Claudia,
Pestalozzi Bernhard,
Chen YaoTseng,
Knuth Alexander,
Jäger Dirk,
Moch Holger
Publication year - 2008
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23241
Subject(s) - messenger rna , biology , exon , microbiology and biotechnology , estrogen receptor , prostate cancer , cancer research , breast cancer , cancer , gene , genetics
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 immunohistochemisty 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 α (ERα) 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 ERα. 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). © 2007 Wiley‐Liss, Inc.