Theurillat Jean-Philippe, Ingold Fabienne, Frei Claudia, Zippelius Alfred, Varga Zsuzsanna, Seifert Burkhardt, Chen Yao-Tseng, Jäger Dirk, Knuth Alexander, Moch Holger
Department Pathology, Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
Int J Cancer. 2007 Jun 1;120(11):2411-7. doi: 10.1002/ijc.22376.
NY-ESO-1 is a cancer testis antigen expressed in various malignancies and testicular germ cells. Because of its capacity to induce specific humoral and cellular immunity in patients with NY-ESO-1-positive carcinomas, it represents a promising target for cancer immunotherapy. In breast cancer, NY-ESO-1-mRNA was reported in up to 42%, but protein expression has not been determined to larger extent. In the present tissue microarray-based study, primary breast cancers (n = 1,444), in situ lesion (n = 148), recurrences (n = 88), lymph node (n = 525) and distant metastases (n = 91) were studied for NY-ESO-1 expression by immunohistochemistry. NY-ESO-1-protein expression was compared with mRNA expression by real-time PCR. NY-ESO-1-protein was detected in 3.1% (4/128) in situ lesions and in 2.1% (28/1355) invasive breast cancer. There were 1.8% (9/493) NY-ESO-1-positive lymph node and 5.1% (4/78) positive distant metastases. NY-ESO-1 was more frequently expressed in grade 3 (4.9%) than in grade 2 (0.8%) and grade 1 (0.5%) carcinomas (p < 0.0001). Presence of tumor-infiltrating CD8+ T-cells correlated with NY-ESO-1 (p < 0.0001) on the tissue microarray. On randomly selected large sections, 4 out of 9 NY-ESO-1-positive tumors displayed a brisk infiltrate of CD79a+ plasmocytes/B-cells, but none of 10 NY-ESO-1-negative tumors (p < 0.05). NY-ESO-1-mRNA expression was detected in frozen samples of NY-ESO-1-protein positive (n = 6) and negative breast cancers (n = 8) and in normal testis. Comparison between mRNA and protein expression revealed that only breast cancers with NY-ESO-1-mRNA levels comparable or higher than testis expressed NY-ESO-1-protein. These findings suggest that NY-ESO-1-positive breast cancers represent a small subset of poorly differentiated tumors with evidence of cellular and humoral immune response.
NY-ESO-1是一种癌胚抗原，在多种恶性肿瘤和睾丸生殖细胞中表达。由于其能够在NY-ESO-1阳性癌患者中诱导特异性体液免疫和细胞免疫，它是癌症免疫治疗的一个有前景的靶点。在乳腺癌中，报道称高达42%的病例存在NY-ESO-1-mRNA，但尚未在更大范围内确定其蛋白表达情况。在本基于组织微阵列的研究中，通过免疫组织化学对1444例原发性乳腺癌、148例原位病变、88例复发肿瘤、525例淋巴结和91例远处转移灶进行了NY-ESO-1表达研究。通过实时PCR将NY-ESO-1蛋白表达与mRNA表达进行比较。在3.1%（4/128）的原位病变和2.1%（28/1355）的浸润性乳腺癌中检测到NY-ESO-1蛋白。在1.8%（9/493）的淋巴结和5.1%（4/78）的远处转移灶中检测到NY-ESO-1阳性。NY-ESO-1在3级癌（4.9%）中的表达频率高于2级癌（0.8%）和1级癌（0.5%）（p<0.0001）。在组织微阵列上，肿瘤浸润性CD8+T细胞的存在与NY-ESO-1相关（p<0.0001）。在随机选择的大切片上，9例NY-ESO-1阳性肿瘤中有4例显示CD79a+浆细胞/B细胞的活跃浸润，但10例NY-ESO-1阴性肿瘤中均未显示（p<0.05）。在NY-ESO-1蛋白阳性（n=6）和阴性乳腺癌（n=8）的冷冻样本以及正常睾丸中检测到NY-ESO-1-mRNA表达。mRNA和蛋白表达的比较显示，只有NY-ESO-1-mRNA水平与睾丸相当或高于睾丸的乳腺癌才表达NY-ESO-1蛋白。这些发现表明，NY-ESO-1阳性乳腺癌代表了一小部分低分化肿瘤，具有细胞免疫和体液免疫反应的证据。
