NY-BR-1 protein expression in breast carcinoma: a mammary gland differentiation antigen as target for cancer immunotherapy.
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.
Theurillat
Jean-Philippe
JP
Institute for Surgical Pathology, Department of Pathology, University Hospital Zurich, Schmelzbergstrasse 12, 8091, Zurich, Switzerland. Jean-Philippe.Theurillat@cell.biol.ethz.ch
Zürrer-Härdi
Ursina
U
Varga
Zsuzsanna
Z
Storz
Martina
M
Probst-Hensch
Nicole M
NM
Seifert
Burkhardt
B
Fehr
Mathias K
MK
Fink
Daniel
D
Ferrone
Soldano
S
Pestalozzi
Bernhard
B
Jungbluth
Achim A
AA
Chen
Yao-Tseng
YT
Jäger
Dirk
D
Knuth
Alexander
A
Moch
Holger
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000943:Antigens, Differentiation / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D001943:Breast Neoplasms / Q000145:classification / Q000175:diagnosis / Q000276:immunology*; D002277:Carcinoma / Q000145:classification / Q000175:diagnosis / Q000276:immunology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D016019:Survival Analysis; D046888:Tissue Array Analysis
C509866:ANKRD30A protein, human; D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm