Expression of aberrantly glycosylated Mucin-1 in ovarian cancer
Expression of aberrantly glycosylated Mucin-1 in ovarian cancer
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DOI：
10.1111/j.1365-2559.2010.03667.x
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发表时间：
2010-10-01
期刊：
影响因子：
6.4
通讯作者：
Bos, Gerard M. J.
中科院分区：
文献类型：
--
作者：
Van Elssen, Catharina H. M. J.;Frings, Peter W. H.;Bos, Gerard M. J.
目的：粘蛋白1(MUC1)是一种重要的肿瘤相关抗原(TAA)，在腺癌中过度表达并异常糖化。方法与结果：采用免疫组织化学方法对37例不同组织类型(浆液性22例，粘液性5例，透明细胞2例，子宫内膜样变8例)、4例浆液性交界性肿瘤伴上皮内癌、7例卵巢子宫内膜异位症和13例转移灶的石蜡包埋组织切片进行分析。以非肿瘤性卵巢表面上皮和浆液性囊腺瘤为对照。所有上皮细胞均表达MUC1蛋白。在原发肿瘤中，76%表达与分化相关的糖形式，84%表达与癌相关的糖形式(TN/sialyl-Tn表位)。在转移性病变中，这一比例分别为77%和85%。值得注意的是，57%的卵巢子宫内膜异位症和75%的上皮内病变表达与癌相关的MUC1表位，而正常卵巢表面上皮和浆液性囊腺瘤不表达这些表位。结论：低糖基化的MUC1表位在所有组织类型的原发卵巢腺癌、绝大多数转移性病变和可能的卵巢癌前病变中都有表达，但在正常卵巢组织中不表达。这些结果表明，MUC1相关的Tn/STn表位是卵巢癌患者免疫治疗和诊断成像的重要靶点。
Aims:Mucin 1 (MUC1) is an important tumour-associated antigen (TAA), both overexpressed and aberrantly glycosylated in adenocarcinomas. The aim of this study was to examine the MUC1-glycosylation status of primary ovarian adenocarcinomas and metastatic lesions.Methods and results:Paraffin-embedded tissue sections of 37 primary ovarian adenocarcinomas representing all histotypes (22 serous, five mucinous, two clear-cell, eight endometrioid), four serous borderline tumours with intraepithelial carcinoma, seven sections of ovarian endometriosis and 13 metastatic lesions were analysed by immunohistochemistry. Non-neoplastic ovarian surface epithelium and serous cystadenomas were used as controls. All epithelia expressed MUC1 protein. Of primary tumours, 76% expressed the differentiation-dependent glycoform and 84% the cancer-associated glycoform (Tn/Sialyl-Tn-epitopes). In metastatic lesions this was 77% and 85%, respectively. Notably, in 57% of ovarian endometriosis and 75% of intraepithelial lesions, the cancer-associated MUC1 epitopes were expressed, whereas normal ovarian surface epithelium and serous cystadenomas did not express these epitopes.Conclusions:The underglycosylated MUC1 epitopes are expressed by all histotypes of primary ovarian adenocarcinomas, by the vast majority of metastatic lesions and by possible ovarian cancer precursor lesions, but not by normal ovarian tissue. These results indicate that MUC1-associated Tn/STn-epitopes are important targets for immunotherapy and diagnostic imaging in ovarian cancer patients.