Varga Zsuzsanna, Theurillat Jean-Philippe, Filonenko Valeriy, Sasse Bernd, Odermatt Bernhard, Jungbluth Achim A, Chen Yao-Tseng, Old Lloyd J, Knuth Alexander, Jäger Dirk, Moch Holger
Institute of Surgical Pathology, Department Pathology, University Hospital of Zurich, Zurich, Switzerland.
Clin Cancer Res. 2006 May 1;12(9):2745-51. doi: 10.1158/1078-0432.CCR-05-2192.
NY-BR-1 is a recently isolated differentiation antigen, which is expressed in normal mammary tissue and in breast cancer. However, current data are based on RT-PCR analysis and nothing is known about the presence of NY-BR-1 on a protein level. We previously generated a monoclonal antibody to NY-BR-1 to study the protein expression of NY-BR-1.
In our immunohistochemical study, NY-BR-1 was analyzed in normal tissues, various tumor types, 124 primary breast cancers, and 37 paired lymph node metastases.
Among normal tissues, NY-BR-1 was present solely in ductal epithelium of the breast. In tumors, carcinoma in situ and invasive carcinoma of the breast were NY-BR-1 positive whereas other tumors and normal tissues were negative. Sixty percent of invasive breast carcinomas were NY-BR-1 positive, displaying cytoplasmic and/or nuclear immunoreactivity. This coexpression was verified by confocal microscopy. Although the monoclonal antibody identified intratumoral heterogeneity, a majority (72%) of NY-BR-1-positive carcinomas revealed immunoreactivity in >50% of the tumor cells. NY-BR-1 expression was more frequent in estrogen receptor-positive and lymph node-negative primary carcinomas (P < 0.05 each) and was more common in grade 1 (77%) than in grade 2 (63%) or grade 3 (50%) carcinomas (P < 0.05). This suggests that NY-BR-1 expression is lost with tumor progression. Forty-nine percent of lymph node metastases were NY-BR-1 positive.
This study supports the notion that NY-BR-1 is a differentiation antigen of the breast, which is present in normal and tumorous mammary epithelium. The organ-specific expression of NY-BR-1 and its high prevalence in metastases indicate that it could be a valuable target for cancer immunotherapy.
NY-BR-1是一种最近分离出的分化抗原，在正常乳腺组织和乳腺癌中均有表达。然而，目前的数据基于逆转录聚合酶链反应（RT-PCR）分析，关于NY-BR-1蛋白水平的存在情况尚无定论。我们之前制备了一种针对NY-BR-1的单克隆抗体，以研究NY-BR-1的蛋白表达。
在我们的免疫组织化学研究中，对正常组织、各种肿瘤类型、124例原发性乳腺癌和37对配对淋巴结转移灶进行了NY-BR-1分析。
在正常组织中，NY-BR-1仅存在于乳腺导管上皮中。在肿瘤中，乳腺原位癌和浸润性癌NY-BR-1呈阳性，而其他肿瘤和正常组织为阴性。60%的浸润性乳腺癌NY-BR-1呈阳性，表现为细胞质和/或细胞核免疫反应性。这种共表达通过共聚焦显微镜得到证实。尽管单克隆抗体识别出肿瘤内异质性，但大多数（72%）NY-BR-1阳性癌在>50%的肿瘤细胞中显示免疫反应性。NY-BR-1表达在雌激素受体阳性和淋巴结阴性的原发性癌中更常见（各P<0.05），在1级癌（77%）中比在2级癌（63%）或3级癌（50%）中更常见（P<0.05）。这表明NY-BR-1表达随肿瘤进展而丧失。49%的淋巴结转移灶NY-BR-1呈阳性。
本研究支持NY-BR-1是乳腺的一种分化抗原，存在于正常和肿瘤性乳腺上皮中的观点。NY-BR-1的器官特异性表达及其在转移灶中的高发生率表明它可能是癌症免疫治疗的一个有价值的靶点。
