title: 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.affiliation: Institute for Surgical Pathology, Department of Pathology, University Hospital Zurich, Schmelzbergstrasse 12, 8091, Zurich, Switzerland. Jean-Philippe.Theurillat@cell.biol.ethz.ch
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Theurillat
authors.forename: Ursina
authors.initials: U
authors.lastname: Zürrer-Härdi
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Varga
authors.forename: Martina
authors.initials: M
authors.lastname: Storz
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Probst-Hensch
authors.forename: Burkhardt
authors.initials: B
authors.lastname: Seifert
authors.forename: Mathias K
authors.initials: MK
authors.lastname: Fehr
authors.forename: Daniel
authors.initials: D
authors.lastname: Fink
authors.forename: Soldano
authors.initials: S
authors.lastname: Ferrone
authors.forename: Bernhard
authors.initials: B
authors.lastname: Pestalozzi
authors.forename: Achim A
authors.initials: AA
authors.lastname: Jungbluth
authors.forename: Yao-Tseng
authors.initials: YT
authors.lastname: Chen
authors.forename: Dirk
authors.initials: D
authors.lastname: Jäger
authors.forename: Alexander
authors.initials: A
authors.lastname: Knuth
authors.forename: Holger
authors.initials: H
authors.lastname: Moch
mesh_terms: 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
chemical_list: C509866:ANKRD30A protein, human; D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm