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单克隆抗体MY.1E12识别的MUC1表达是晚期结肠癌肿瘤侵袭性的一个有用生物标志物。

Expression of MUC1 recognized by monoclonal antibody MY.1E12 is a useful biomarker for tumor aggressiveness of advanced colon carcinoma.

作者信息

Suzuki Hideo, Shoda Junichi, Kawamoto Toru, Shinozaki Eiji, Miyahara Naoki, Hotta Souichi, Iizuka Yasushi, Nakahara Akira, Tanaka Naomi, Yanaka Akinori, Irimura Tatsuro

机构信息

Department of Gastroenterology, Institute of Clinical Medicine, The University of Tsukuba, Tsukuba-shi, Ibaraki, Japan.

出版信息

Clin Exp Metastasis. 2004;21(4):321-9. doi: 10.1023/b:clin.0000046133.35133.cc.

DOI:10.1023/b:clin.0000046133.35133.cc
PMID:15554388
Abstract

To address the need for new prognostic parameters in advanced colon carcinoma that could add insights into the aggressiveness of tumors, the expression levels of MUC1 recognized by a monoclonal antibody (mAb) MY.1E12 in archival specimens from 123 Japanese patients with colon carcinomas were evaluated by immunohistochemistry to correlate the results with clinicopathological characteristics. The localization of mAb MY.1E12-reactive-MUC1 (MY.1E12-MUC1) was classified into apical, cytoplasmic and stromal types based on the predominant cellular distribution. The MUC1 mRNA levels revealed by in situ hybridization were not a determinant for the localization types of MY.1E12-MUC1. Immunostaining of MY.1E12-MUC1 was recognized in the cancerous epithelia of pT1 carcinoma in 61%, pT2 in 78%, pT3 in 98% and pT4 in 90% of the cases at the deepest invading sites. At the deepest invading sites, apical-type localization was found to predominate in pT1 carcinoma, but stromal-type localization was found to increase in pT2-4 carcinomas in parallel with the depth of invasion. The frequency of synchronous distant organ metastasis at the time of diagnosis tended to be higher in cases of pT3 and pT4 carcinomas in the stromal-type localization-dominant group than in cases in the apical-type localization-dominant group. The post-surgical survival outcome of cases of pT3 and pT4 carcinomas was significantly poorer in the former than in the latter (P = 0.002). The stromal-type localization of MY.1E12-MUC1 may be a phenotype serving as a unique biological feature associated with the tumor aggressiveness of advanced colon carcinoma.

摘要

为了满足晚期结肠癌新预后参数的需求,以便深入了解肿瘤的侵袭性,通过免疫组织化学评估了123例日本结肠癌患者存档标本中由单克隆抗体(mAb)MY.1E12识别的MUC1表达水平,并将结果与临床病理特征相关联。基于主要细胞分布,将mAb MY.1E12反应性MUC1(MY.1E12-MUC1)的定位分为顶端型、胞质型和基质型。原位杂交显示的MUC1 mRNA水平不是MY.1E12-MUC1定位类型的决定因素。在最深浸润部位,61%的pT1癌、78%的pT2癌、98%的pT3癌和90%的pT4癌的癌上皮中可识别出MY.1E12-MUC1免疫染色。在最深浸润部位,顶端型定位在pT1癌中占主导,但在pT2-4癌中,基质型定位随着浸润深度增加。基质型定位占主导的pT3和pT4癌病例在诊断时同步远处器官转移的频率往往高于顶端型定位占主导的病例。pT3和pT4癌病例的术后生存结果在前一组中明显比后一组差(P = 0.002)。MY.1E12-MUC1的基质型定位可能是一种表型,作为与晚期结肠癌肿瘤侵袭性相关的独特生物学特征。

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本文引用的文献

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Expression of MUC1 recognized by a monoclonal antibody MY.1E12 is a useful biomarker for tumor aggressiveness of carcinoma of the gallbladder.单克隆抗体MY.1E12识别的MUC1表达是胆囊癌肿瘤侵袭性的一个有用生物标志物。
Clin Exp Metastasis. 2004;21(4):353-62. doi: 10.1023/b:clin.0000046177.70405.cb.
2
Tumor necrosis factor-alpha converting enzyme/ADAM 17 mediates MUC1 shedding.肿瘤坏死因子-α转化酶/去整合素-金属蛋白酶17介导MUC1脱落。
J Biol Chem. 2003 Jan 31;278(5):3386-94. doi: 10.1074/jbc.M208326200. Epub 2002 Nov 18.
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The epitope recognized by the unique anti-MUC1 monoclonal antibody MY.1E12 involves sialyl alpha 2-3galactosyl beta 1-3N-acetylgalactosaminide linked to a distinct threonine residue in the MUC1 tandem repeat.
结直肠癌肝转移灶切除术后使用替西莫肽进行辅助性MUC疫苗接种:一项随机、双盲、安慰剂对照、多中心AIO II期试验(LICC)
Oncoimmunology. 2020 Aug 23;9(1):1806680. doi: 10.1080/2162402X.2020.1806680.
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Molecular fluorescence-guided surgery of peritoneal carcinomatosis of colorectal origin: A narrative review.结直肠源性腹膜癌病的分子荧光引导手术:一项叙述性综述。
J Surg Oncol. 2018 Aug;118(2):332-343. doi: 10.1002/jso.25106. Epub 2018 Jun 24.
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Intra- and Extra-Cellular Events Related to Altered Glycosylation of MUC1 Promote Chronic Inflammation, Tumor Progression, Invasion, and Metastasis.与MUC1糖基化改变相关的细胞内和细胞外事件促进慢性炎症、肿瘤进展、侵袭和转移。
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7
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Expression of MUC1 and MUC2 mucin antigens in intrahepatic bile duct tumors: its relationship with a new morphological classification of cholangiocarcinoma.MUC1和MUC2黏蛋白抗原在肝内胆管肿瘤中的表达:其与胆管癌新形态学分类的关系
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