Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-4111
Theurillat, J P; Zürrer-Härdi, U; Varga, Z; Barghorn, A; Saller, E; Frei, C; Storz, M; Behnke, S; Seifert, Burkhardt; Fehr, M; Fink, D; Rageth, C; Linsenmeier, C; Pestalozzi, B; Chen, Y T; Knuth, A; Jäger, D; Moch, H (2008). Distinct expression patterns of the immunogenic differentiation antigen NY-BR-1 in normal breast, testis and their malignant counterparts. International Journal of Cancer, 122(7):1585-1591.
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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).
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Institute of Social and Preventive Medicine|
04 Faculty of Medicine > University Hospital Zurich > Clinic for Gynecology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Oncology
04 Faculty of Medicine > University Hospital Zurich > Institute of Surgical Pathology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Radiation Oncology
|DDC:||610 Medicine & health|
|Deposited On:||14 Nov 2008 14:04|
|Last Modified:||24 Mar 2014 07:45|
|Citations:||Web of Science®. Times Cited: 6|
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