Distinct expression patterns of the immunogenic differentiation antigen NY-BR-1 in normal breast, testis and their malignant counterparts.
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).
Institute of Surgical Pathology, Department Pathology, University Hospital of Zürich, Switzerland. jean-philippe.theurillat@cell.biol.ethz.ch
Jean-Philippe
JP
Theurillat
Ursina
U
Zürrer-Härdi
Zsuzsanna
Z
Varga
André
A
Barghorn
Elisabeth
E
Saller
Claudia
C
Frei
Martina
M
Storz
Silvia
S
Behnke
Burkhardt
B
Seifert
Mathias
M
Fehr
Daniel
D
Fink
Christoph
C
Rageth
Claudia
C
Linsenmeier
Bernhard
B
Pestalozzi
Yao-Tseng
YT
Chen
Alexander
A
Knuth
Dirk
D
Jäger
Holger
H
Moch
D000951:Antigens, Neoplasm / Q000032:analysis* / Q000235:genetics; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D001940:Breast / Q000276:immunology*; D001943:Breast Neoplasms / Q000276:immunology*; D020847:Estrogen Receptor Modulators / Q000627:therapeutic use; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D011471:Prostatic Neoplasms / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D011960:Receptors, Estrogen / Q000378:metabolism; D020218:Response Elements; D013629:Tamoxifen / Q000627:therapeutic use; D013736:Testicular Neoplasms / Q000276:immunology*; D013737:Testis / Q000276:immunology*
C509866:ANKRD30A protein, human; D000951:Antigens, Neoplasm; D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D020847:Estrogen Receptor Modulators; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D013629:Tamoxifen