Matsushita Norihiro, Ghazizadeh Mohammad, Konishi Hideki, Araki Tsutomu
Department of Obstetrics and Gynecology, Nippon Medical School, Kanagawa, Japan.
J Nippon Med Sch. 2003 Feb;70(1):40-4. doi: 10.1272/jnms.70.40.
Understanding of the relationship between tumor infiltrating cytotoxic T lymphocytes (CD 8(+)TILs) and tumor cells as well as tumor-associated antigens is important and may reflect the extent of immune response of the patient to the tumor, thus providing a useful clue relevant to the prognosis. The purpose of this study was to determine the relationship between the expression of HLA-DR and CA-125 antigens and the presence of CD 8(+)TILs with regard to the established clinicopathological factors of ovarian carcinomas using immunohistochemical methods. Thirty-one ovarian carcinomas consisting of 20 serous, 7 mucinous, and 4 clear cell types were examined. Of these, 18 (58%) and 22 (71%) were positive for HLA-DR and CA-125 antigens respectively, and the overall mean number of the CD 8(+)TILs was 7.2+/-2.9. A significant association was observed between the mean number of CD8(+)TILs and tumor grade (P=0.01), disease stage (P=0.003), and patient outcome (P=0.01). The mean number of CD 8(+)TILs in HLA-DR positive (8.6+/-2.2) or CA-125 positive (8.4+/-2.1) tumors was significantly higher than that in HLA-DR negative (5.2+/-2.5; P=0.0003) or CA-125 negative (4.2+/-2.2; P=0.00002) tumors. These significant levels were further enhanced by one order of magnitude when the mean number of CD 8(+)TILs in tumors positive for both HLA-DR and CA-125 antigens (9.1+/-1.7) was compared to that in HLA-DR negative or CA-125 negative tumors. The frequency of cancer-related deaths in HLA-DR and CA-125 positive tumors was significantly lower than in the negative tumors (P=0.01). These data suggest that concurrent expression of HLA-DR and CA-125 antigens may augment the immune response of the patient to the tumor, thus providing a potential clue relevant to the prognosis.
了解肿瘤浸润性细胞毒性T淋巴细胞（CD8(+)肿瘤浸润淋巴细胞）与肿瘤细胞以及肿瘤相关抗原之间的关系非常重要，这可能反映患者对肿瘤的免疫反应程度，从而为判断预后提供有用线索。本研究的目的是采用免疫组织化学方法，确定HLA-DR和CA-125抗原的表达与CD8(+)肿瘤浸润淋巴细胞的存在之间的关系，以及它们与卵巢癌既定临床病理因素的关系。研究检查了31例卵巢癌，其中包括20例浆液性、7例黏液性和4例透明细胞型。其中，18例（58%）和22例（71%）分别对HLA-DR和CA-125抗原呈阳性反应，CD8(+)肿瘤浸润淋巴细胞的总体平均数为7.2±2.9。观察到CD8(+)肿瘤浸润淋巴细胞的平均数与肿瘤分级（P=0.01）、疾病分期（P=0.003）和患者预后（P=0.01）之间存在显著关联。HLA-DR阳性（8.6±2.2）或CA-125阳性（8.4±2.1）肿瘤中CD8(+)肿瘤浸润淋巴细胞的平均数显著高于HLA-DR阴性（5.2±2.5；P=0.0003）或CA-125阴性（4.2±2.2；P=0.00002）肿瘤。当将HLA-DR和CA-125抗原均呈阳性的肿瘤中CD8(+)肿瘤浸润淋巴细胞的平均数（9.1±1.7）与HLA-DR阴性或CA-125阴性肿瘤进行比较时，这些显著水平又提高了一个数量级。HLA-DR和CA-125阳性肿瘤中与癌症相关的死亡频率显著低于阴性肿瘤（P=0.01）。这些数据表明，HLA-DR和CA-125抗原的同时表达可能增强患者对肿瘤的免疫反应，从而为判断预后提供潜在线索。
