Department of Molecular Biosciences, Faculty of Life Sciences, Kyoto Sangyo University, Kamigamo-Motoyama, Kyoto, Japan.
Int J Gynecol Cancer. 2012 May;22(4):531-8. doi: 10.1097/IGC.0b013e3182473292.
Although CA125 antigen is a useful marker for ovarian cancer, its expression is also elevated in endometriosis. The purpose of this study was to develop an assay method for evaluating differentially glycosylated MUC16 (CA125 core protein) in patients with endometriosis and ovarian cancer.
We prepared MUC16-enriched fractions from peritoneal fluid of patients with endometriosis and conditioned medium of ovarian carcinoma-3 cells by gel filtration, and evaluated the expression of sialyl-Le, Tn, and sialyl-Tn antigens by dot blot analysis. A sandwich enzyme-linked immunosorbent assay was developed to measure the level of sialyl-Tn antigen expressed on MUC16 (sTn/MUC16). The level of sTn/MUC16 was compared between patients with endometriosis (n = 21) and ovarian cancer (n = 36) and in ovarian cancers with different clinical diagnostic criteria. Furthermore, distribution of MUC16 and sialyl-Tn antigen in ovarian cancer tissues was observed immunohistochemically.
Sialyl-Tn antigen was markedly detectable in the MUC16-enriched fractions from conditioned medium of ovarian carcinoma-3 cells but negligible in those from the peritoneal fluid of the patients with endometriosis. The level of sTn/MUC16 determined by a sandwich enzyme-linked immunosorbent assay was significantly higher in the patients with ovarian cancer than that in the patients with endometriosis (P < 0.001). An elevated level of sTn/MUC16 was detected in 44% of the patients with ovarian cancer but not all the patients with endometriosis. This level increased more prominently in the patients with ovarian cancer than that of MUC16 as both the clinical stage and cytological grade advanced. An elevated level of sTn/MUC16 was frequently found in the patients with serous and endometrioid carcinomas. Consistent with this, sialyl-Tn antigen was colocalized with MUC16 in serous and endometrioid ovarian cancer tissues.
Estimation of the sTn/MUC16 level may be useful for discriminating endometriosis from ovarian cancer and for evaluating the clinical stage, cytological grade, and histological type of ovarian cancer.
尽管 CA125 抗原是一种用于诊断卵巢癌的有用标志物，但它在子宫内膜异位症中也有表达升高。本研究旨在开发一种评估子宫内膜异位症和卵巢癌患者中差异糖基化 MUC16（CA125 核心蛋白）的检测方法。
我们通过凝胶过滤从子宫内膜异位症患者的腹腔液和卵巢癌-3 细胞的条件培养基中制备 MUC16 富集级分，并通过斑点印迹分析评估唾液酸化-Le、Tn 和唾液酸化-Tn 抗原的表达。我们开发了一种夹心酶联免疫吸附试验来测量 MUC16 上表达的唾液酸化-Tn 抗原（sTn/MUC16）的水平。比较了 21 例子宫内膜异位症患者和 36 例卵巢癌患者之间 sTn/MUC16 的水平，以及不同临床诊断标准的卵巢癌之间 sTn/MUC16 的水平。此外，我们通过免疫组织化学观察卵巢癌组织中 MUC16 和唾液酸化-Tn 抗原的分布。
在卵巢癌-3 细胞条件培养基的 MUC16 富集级分中，唾液酸化-Tn 抗原明显可检测到，但在子宫内膜异位症患者的腹腔液中则检测不到。夹心酶联免疫吸附试验测定的 sTn/MUC16 水平在卵巢癌患者中显著高于子宫内膜异位症患者（P < 0.001）。在 44%的卵巢癌患者中检测到 sTn/MUC16 水平升高，但并非所有子宫内膜异位症患者均升高。随着卵巢癌临床分期和细胞学分级的进展，sTn/MUC16 水平升高更为显著。在浆液性和子宫内膜样癌患者中，sTn/MUC16 水平升高更为常见。与此一致，唾液酸化-Tn 抗原与浆液性和子宫内膜样卵巢癌组织中的 MUC16 共定位。
估计 sTn/MUC16 水平可能有助于鉴别子宫内膜异位症和卵巢癌，并评估卵巢癌的临床分期、细胞学分级和组织学类型。
