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

Theurillat, Jean-Philippe ; Zürrer-Härdi, Ursina ; Varga, Zsuzsanna ; Storz, Martina ; Probst-Hensch, Nicole ; Seifert, Burkhardt ; Fehr, Mathias ; Fink, Daniel ; Ferrone, Soldano ; Pestalozzi, Bernhard ; Jungbluth, Achim ; Chen, Yao-Tseng ; Jäger, Dirk ; Knuth, Alexander ; Moch, Holger

In: Cancer Immunology, Immunotherapy, 2007, vol. 56, no. 11, p. 1723-1731

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    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 (κ=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