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[紧密连接蛋白-1、3和4在结直肠癌及息肉中的表达]

[Еxpression of claudin-1, 3, and 4 in colorectal cancer and polyps].

作者信息

Nefedova N А, Kharlova О А, Malkov P G

机构信息

Russian Medical Academy of Postgraduate Education Ministry of Health of Russia, Moscow; Lomonosov Moscow State University, Moscow, Russia.

Lomonosov Moscow State University, Moscow, Russia.

出版信息

Arkh Patol. 2016 May-Jun;78(3):11-19. doi: 10.17116/patol201678311-19.

Abstract

UNLABELLED

Claudins are a family of transmembrane tight junctions proteins. It is proven that claudins undergo structural and functional alteration in malignant cells. However, very few researches are pursued on this topic, the data provided by different researchers are controversial. The aim of this study was to evaluate expression of tight junction proteins in cancer and benign polyps of the colon and rectum.

MATERIAL AND METHODS

Specimens of 32 colorectal adenocarcinomas and biopsy specimens of 86 polypoid lesions of the colon and rectum were selected from diagnostic material. Polyps were divided into 6 groups following the 2010 WHO classification of premalignant lesions of the colon and rectum. Immunohistochemical labeling with claudin-1, claudin-3 and claudin-4 antibodies was performed in all cases. We used G. Sheehan et al. (2007) method to evaluate the expression of claudins in neoplasm as well as in adjacent normal mucosa in each slide.

RESULTS

Immunohistochemical staining with claudins antibodies had membranous pattern; claudins expression in adjacent normal mucosa was uniformly close to maximum. Serrated lesions showed the lowest level of expression of claudin-1 among other groups (p<0,05). In the group of adenocarcinomas we found moderate negative correlation between claudin-1 expression level and grade of adenocarcinoma. Claudin-3 expression level was significantly higher in adenocarcinomas compared to serrated lesions (p=0,025) and in conventional adenomas compared to serrated lesions (p=0,034). Expression of claudin-4 was strong in most cases, except for tubular adenomas that showed moderate expression in most cases.

CONCLUSION

We found no statistically significant difference between levels of expression of claudin-1, claudin-3 and claudin-4 expression levels among adenocarcinomas, hyperplastic polyps, sessile serrated adenomas, traditional serrated adenomas, tubular and tubular-villous adenomas. But we detected significant difference after enlargement of the groups. This fact may argue for general development pathway of hyperplastic polyps and sessile serrated adenomas, and of tubular and tubular-villous adenomas. Expression of claudin-1 and claudin-3 revealed difference of serrated lesions from conventional adenomas and adenocarcinomas, that confirms conception of independent «serrated» pathway of cancerogenesis.

摘要

未标记

紧密连接蛋白是一类跨膜紧密连接蛋白家族。已证实紧密连接蛋白在恶性细胞中会发生结构和功能改变。然而,关于这一主题的研究非常少,不同研究者提供的数据存在争议。本研究的目的是评估紧密连接蛋白在结直肠癌和结直肠良性息肉中的表达情况。

材料与方法

从诊断材料中选取32例结直肠癌标本和86例结直肠息肉样病变的活检标本。根据2010年世界卫生组织对结直肠前驱病变的分类,将息肉分为6组。所有病例均采用紧密连接蛋白-1、紧密连接蛋白-3和紧密连接蛋白-4抗体进行免疫组织化学标记。我们采用G. Sheehan等人(2007年)的方法评估每张切片中肿瘤组织以及相邻正常黏膜中紧密连接蛋白的表达情况。

结果

紧密连接蛋白抗体免疫组织化学染色呈膜性模式;相邻正常黏膜中紧密连接蛋白的表达均接近最大值。锯齿状病变组中紧密连接蛋白-1的表达水平在其他组中最低(p<0.05)。在腺癌组中,我们发现紧密连接蛋白-1的表达水平与腺癌分级之间存在中度负相关。与锯齿状病变相比,腺癌中紧密连接蛋白-3的表达水平显著更高(p=0.025),与锯齿状病变相比,传统腺瘤中紧密连接蛋白-3的表达水平也显著更高(p=0.034)。除大多数管状腺瘤呈中度表达外,紧密连接蛋白-4在大多数情况下表达较强。

结论

我们发现腺癌、增生性息肉、无蒂锯齿状腺瘤、传统锯齿状腺瘤、管状腺瘤和管状绒毛状腺瘤之间紧密连接蛋白-1、紧密连接蛋白-3和紧密连接蛋白-4的表达水平无统计学显著差异。但扩大分组后我们检测到了显著差异。这一事实可能支持增生性息肉和无蒂锯齿状腺瘤以及管状腺瘤和管状绒毛状腺瘤的一般发展途径。紧密连接蛋白-1和紧密连接蛋白-3的表达揭示了锯齿状病变与传统腺瘤和腺癌的差异,这证实了独立的“锯齿状”癌变途径的概念。

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