NY-BR-1 protein expression in breast carcinoma: a mammary gland differentiation antigen as target for cancer immunotherapy.

Abstract

NY-BR-1 is a recently identified differentiation antigen of the mammary gland. To use NY-BR-1 for T-cell-based immunotherapy, analysis of its co-expression with HLA class I antigens is required. In the present tissue microarray study, primary breast cancers (n = 1,444), recurrences (n = 88), lymph node (n = 525) and distant metastases (n = 91) were studied for NY-BR-1 expression using a novel monoclonal antibody. NY-BR-1 expression was compared with prognosis, estrogen receptor, HER2-status, EGFR and HLA class I antigen expression. NY-BR-1 was more frequently expressed in grade 1 (82%) than in grade 2 (69%) and grade 3 (46%) carcinomas (P < 0.0001). Moreover, NY-BR-1 expression correlated directly with estrogen receptor expression (P < 0.0001) and inversely correlated with HER2-status and EGFR expression (P < 0.0001 for both). Considering high expression level of co-expression, 198/1,321 (15%) primary breast carcinomas and 4/65 (6%) distant metastases expressed NY-BR-1 and HLA class I, suggesting that active immunotherapy can be applied to about 10% of breast cancer patients. Survival analysis showed an association of NY-BR-1 expression with better patient outcome (P = 0.015). No difference between NY-BR-1 expression of primary tumors and metastases could be found, indicating that the presence of NY-BR-1 in metastases can be deduced from their corresponding primary. Forty-three paired biopsies taken from patients before and after chemotherapy suggest that NY-BR-1 expression is not influenced by preceding chemotherapy (kappa = 0.89, P < 0.0001). In summary, the co-expression of NY-BR-1 with HLA class I antigens and its expression in metastases without modification by chemotherapy suggest that NY-BR-1 targeted immunotherapy represents a viable strategy in addition to other targeted cancer drug therapies of breast cancer.

• Authors: Jean-Philippe Theurillat, Ursina Zürrer-Härdi, Zsuzsanna Varga, Martina Storz, Nicole M Probst-Hensch, Burkhardt Seifert, Mathias K Fehr, Daniel Fink, Soldano Ferrone, Bernhard Pestalozzi, Achim A Jungbluth, Yao-Tseng Chen, Dirk Jäger, Alexander Knuth, Holger Moch
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 56 Issue 11 Pg. 1723-31 (Nov 2007) ISSN: 0340-7004 [Print] Germany
• PMID: 17410359 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• ANKRD30A protein, human
• Antigens, Differentiation
• Antigens, Neoplasm

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antigens, Differentiation (drug effects, immunology, metabolism)
• Antigens, Neoplasm (drug effects, immunology, metabolism)
• Breast Neoplasms (classification, diagnosis, immunology)
• Carcinoma (classification, diagnosis, immunology)
• Cell Line, Tumor
• Female
• Humans
• Immunohistochemistry
• Immunotherapy
• Middle Aged
• Predictive Value of Tests
• Prognosis
• Survival Analysis
• Tissue Array Analysis