Utsunomiya Tohru, Inoue Hiroshi, Tanaka Fumiaki, Yamaguchi Hiroshi, Ohta Mitsuhiko, Okamoto Masahiro, Mimori Koshi, Mori Masaki
Department of Surgery, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumibaru, Beppu 874-0838, Japan.
Ann Surg Oncol. 2004 Oct;11(10):934-40. doi: 10.1245/ASO.2004.01.029.
Cancer-testis antigens (CTA), such as MAGE, are selectively expressed in various types of human neoplasms but not in normal tissues other than testis. This characteristic feature of CTA makes them promising antigens for cancer-specific immunotherapy.
We investigated the expression of five genes, including MAGE-1, MAGE-3, NY-ESO-1, SCP-1, and SSX-4, in 20 surgical samples of intrahepatic cholangiocarcinomas (IHCC) using reverse transcription-polymerase chain reaction. To visualize the localization of MAGE proteins, we performed immunohistochemical studies. Furthermore, the correlation between the CTA expression and DNA methylation status was studied in three bile duct cancer cell lines.
Expression of MAGE-1, MAGE-3, NY-ESO-1, SCP-1, and SSX-4 was recognized in 4, 4, 2, 6, and 3 of all 20 cases, respectively. In contrast, the expressions of five genes were not recognized at all in the corresponding normal tissues. In 10 cases (50%), the tumors expressed at least one of the five CTA. An immunohistochemical analysis of MAGE proteins demonstrated homogenous or focal distributions in cytoplasm of the IHCC. Using a demethylating agent, MAGE-1, NY-ESO-1, SCP-1, and SSX-4 were induced in two of three cell lines, whereas MAGE-3 was not.
Half of the tumor tissues of IHCC expressed at least one of the CTA. Some of the patients with IHCC, therefore, should be candidates for potentially useful cancer-specific immunotherapy.
癌-睾丸抗原(CTA),如黑色素瘤抗原基因(MAGE),在各种类型的人类肿瘤中选择性表达,但在睾丸以外的正常组织中不表达。CTA的这一特征使其成为癌症特异性免疫治疗中有前景的抗原。
我们使用逆转录-聚合酶链反应研究了包括MAGE-1、MAGE-3、纽约食管鳞状细胞癌-1(NY-ESO-1)、精子相关抗原1(SCP-1)和滑膜肉瘤X染色体易位基因4(SSX-4)在内的五个基因在20例肝内胆管癌(IHCC)手术样本中的表达。为了观察MAGE蛋白的定位,我们进行了免疫组织化学研究。此外,在三种胆管癌细胞系中研究了CTA表达与DNA甲基化状态之间的相关性。
在所有20例病例中,分别有4例、4例、2例、6例和3例检测到MAGE-1、MAGE-3、NY-ESO-1、SCP-1和SSX-4的表达。相比之下,在相应的正常组织中未检测到这五个基因的表达。在10例(50%)病例中,肿瘤表达了至少一种CTA。对MAGE蛋白的免疫组织化学分析显示,其在IHCC细胞质中呈均匀或局灶性分布。使用去甲基化剂后,在三种细胞系中的两种中诱导出了MAGE-1、NY-ESO-1、SCP-1和SSX-4,而MAGE-3未被诱导。
一半的IHCC肿瘤组织表达了至少一种CTA。因此,一些IHCC患者应成为潜在有用的癌症特异性免疫治疗候选者。