Theurillat Jean-Philippe, Zürrer-Härdi Ursina, Varga Zsuzsanna, Storz Martina, Probst-Hensch Nicole M, Seifert Burkhardt, Fehr Mathias K, Fink Daniel, Ferrone Soldano, Pestalozzi Bernhard, Jungbluth Achim A, Chen Yao-Tseng, Jäger Dirk, Knuth Alexander, Moch Holger
Institute for Surgical Pathology, Department of Pathology, University Hospital Zurich, Schmelzbergstrasse 12, 8091, Zurich, Switzerland.
Cancer Immunol Immunother. 2007 Nov;56(11):1723-31. doi: 10.1007/s00262-007-0316-1. Epub 2007 Apr 5.
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.
NY-BR-1是一种最近发现的乳腺分化抗原。为了将NY-BR-1用于基于T细胞的免疫治疗，需要分析其与HLA I类抗原的共表达情况。在当前的组织芯片研究中，使用一种新型单克隆抗体对1444例原发性乳腺癌、88例复发病例、525例淋巴结和91例远处转移病例进行了NY-BR-1表达研究。将NY-BR-1表达与预后、雌激素受体、HER2状态、表皮生长因子受体（EGFR）和HLA I类抗原表达进行了比较。NY-BR-1在1级癌（82%）中的表达频率高于2级癌（69%）和3级癌（46%）（P<0.0001）。此外，NY-BR-1表达与雌激素受体表达直接相关（P<0.0001），与HER2状态和EGFR表达呈负相关（两者均为P<0.0001）。考虑到共表达的高表达水平，1321例原发性乳腺癌中有198例（15%）和65例远处转移中有4例（6%）表达NY-BR-1和HLA I类，这表明主动免疫治疗可应用于约10%的乳腺癌患者。生存分析显示NY-BR-1表达与患者较好的预后相关（P=0.015）。未发现原发性肿瘤和转移灶的NY-BR-1表达有差异，这表明转移灶中NY-BR-1的存在可从其相应的原发灶推断出来。43例患者化疗前后的配对活检表明，NY-BR-1表达不受先前化疗的影响（kappa=0.89，P<0.0001）。总之，NY-BR-1与HLA I类抗原的共表达及其在转移灶中的表达不受化疗影响，这表明除乳腺癌的其他靶向抗癌药物治疗外，NY-BR-1靶向免疫治疗是一种可行的策略。
