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异常糖基化黏蛋白-1 在卵巢癌中的表达。

Expression of aberrantly glycosylated Mucin-1 in ovarian cancer.

机构信息

Department of Internal Medicine, Division of Haematology, Maastricht University Medical Center, Maastricht, the Netherlands.

出版信息

Histopathology. 2010 Oct;57(4):597-606. doi: 10.1111/j.1365-2559.2010.03667.x.

DOI:10.1111/j.1365-2559.2010.03667.x
PMID:20955385
Abstract

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.

摘要

目的

黏蛋白 1(MUC1)是一种重要的肿瘤相关抗原(TAA),在腺癌中过度表达和异常糖基化。本研究旨在研究原发性卵巢腺癌和转移病灶中 MUC1 糖基化状态。

方法和结果

对 37 例原发性卵巢腺癌组织石蜡切片进行了分析,这些组织代表了所有组织类型(22 例浆液性、5 例黏液性、2 例透明细胞性、8 例子宫内膜样)、4 例伴上皮内癌的浆液性交界性肿瘤、7 例卵巢子宫内膜异位症和 13 例转移病灶。非肿瘤性卵巢表面上皮和浆液性囊腺瘤作为对照。所有上皮均表达 MUC1 蛋白。在原发性肿瘤中,76%表达分化依赖性糖型,84%表达癌症相关糖型(Tn/唾液酸-Tn-表位)。在转移病灶中,分别为 77%和 85%。值得注意的是,在 57%的卵巢子宫内膜异位症和 75%的上皮内病变中,表达了癌症相关的 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

低聚糖基化的 MUC1 表位在所有原发性卵巢腺癌组织类型、绝大多数转移病灶以及可能的卵巢癌前病变中表达,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标。

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