Paneth cell differentiation in colonic epithelial neoplasms: evidence for the role of the Apc/β-catenin/Tcf pathway
Paneth cell differentiation in colonic epithelial neoplasms: evidence for the role of the Apc/β-catenin/Tcf pathway
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DOI：
10.1016/j.humpath.2008.12.003
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发表时间：
2009-06-01
期刊：
影响因子：
3.3
通讯作者：
Odze, Robert D.
中科院分区：
文献类型：
--
作者：
Joo, Mee;Shahsafaei, Aliakbar;Odze, Robert D.
潘氏细胞分化可能发生在结肠上皮肿瘤。然而，它的意义和发展机制仍不清楚。人防御素5是潘氏细胞的特异性标志物，并且已显示代表Apc/β-连环蛋白/Tcf途径的靶基因之一。本研究的目的是评估各种结肠肿瘤中潘氏细胞分化的频率，并研究人防御素5和β-连环蛋白在此过程中的作用。在29例非肿瘤性结肠粘膜、18例增生性息肉、10例无蒂锯齿状腺瘤、12例传统锯齿状腺瘤、21例混合性息肉、39例常规腺瘤和40例腺癌中评价了临床和病理结果，包括潘氏细胞分化的组织学证据和人类防御素5和β-连环蛋白的免疫染色。评估了人类防御素-5和β-连环蛋白表达在所有细胞类型（发育不良和非发育不良）中的位置和染色程度，并与所有类型息肉中Paneth细胞分化的组织学区域相关。在15例常规腺瘤（38.5%）和1例腺癌（2.5%）中观察到潘氏细胞分化的组织学证据，但在其他类型的息肉中未观察到。所有非肿瘤性Paneth细胞和所有肿瘤性Paneth细胞分化为Paneth细胞的细胞质中均可见人防御素-5免疫染色阳性。人类防御素-5在0%的增生性息肉、10%的无蒂锯齿状腺瘤、25%的传统锯齿状腺瘤、33.3%的混合性息肉、82.1%的传统腺瘤和17.5%的腺癌中表达：与所有其他组相比，人类防御素5在传统腺瘤中的表达显著更高（P <0.01）。17例（53.1%）人防御素5阳性的常规腺瘤，6例（86%）人防御素5阳性的腺癌，所有人防御素5阳性的无蒂锯齿状腺瘤，传统锯齿状腺瘤，混合性息肉没有显示潘氏细胞分化的组织学证据。所有显示人防御素5表达的混合性息肉（100%）（7例; 33.3%）显示常规的异型增生。在阳性混合性息肉病例中，人类防御素5仅在常规不典型增生区域呈阳性。在31例具有核β-连环蛋白染色的常规腺瘤中，15例（48.4%）显示了Paneth细胞分化的组织学证据，所有具有Paneth细胞分化的肿瘤细胞均显示核β-连环蛋白染色，而非肿瘤性Paneth细胞始终显示正常的膜β-连环蛋白染色模式。在常规腺瘤和混合性息肉的常规异型增生上皮中，人防御素5表达和核β-连环蛋白表达之间存在很强的地形相关性。潘氏细胞分化在早期结肠肿瘤中是常见的，这些肿瘤通过传统的腺瘤-癌致癌途径发展。Apc/beta-catenin/Tcf通路的激活可能在人结肠肿瘤Paneth细胞分化中起作用。(C)2009 Elsevier Inc. All rights reserved.
Paneth cell differentiation may occur in colonic epithelial neoplasms. However, its significance and mechanism of development remains unclear. Human defensin 5 is a specific marker of Paneth cells and has been shown to represent one of the target genes of the Apc/beta-Catenin/Tcf pathway. The aim of this study was to evaluate the frequency of Paneth cell differentiation in a variety of colonic neoplasms, and to investigate the role of human defensin 5 and beta-catenin in this process. The clinical and pathologic findings, including histologic evidence of Paneth cell differentiation and immunostaining for human defensin 5 and beta-catenin, were evaluated in 29 samples of nonneoplastic colonic mucosa, 18 hyperplastic polyps, 10 sessile serrated adenomas, 12 traditional serrated adenomas, 21 mixed polyps, 39 conventional adenomas, and 40 adenocarcinomas. Human defensin-5 and beta-catenin expression were evaluated for the location and degree of staining in all cell types (dysplastic and nondysplastic) and correlated with histologic areas of Paneth cell differentiation in all types of polyps. Histologic evidence of Paneth cell differentiation was observed in 15 conventional adenomas (38.5%) and 1 adenocarcinoma (2.5%) but not in other types of polyps. Human defensin-5 immunostaining was positive in the cytoplasm of all nonneoplastic Paneth cells and all neoplastic cells with Paneth cell differentiation. Human defensin-5 expression was noted in 0% of hyperplastic polyps, 10% of sessile serrated adenomas, 25% of traditional serrated adenomas, 33.3% of mixed polyps, 82.1% of conventional adenomas, and 17.5% of adenocarcinomas: human defensin 5 expression was significantly higher in conventional adenomas compared to all other groups (P < .01). Seventeen (53.1%) of 32 human defensin 5 positive conventional adenomas, 6 (86%) of 7 of human defensin 5 positive adenocarcinomas, and all human defensin 5-positive sessile serrated adenomas, traditional serrated adenomas, and mixed polyps did not show histologic evidence of Paneth cell differentiation. All mixed polyps (100%) that revealed human defensin 5 expression (7; 33.3%) revealed conventional dysplasia. In the positive mixed polyp cases, human defensin 5 was only positive in areas of conventional dysplasia. Of the 31 conventional adenomas with nuclear beta-catenin staining, 15 (48.4%) revealed histologic evidence of Paneth cell differentiation, and all of the neoplastic cells with Paneth cell differentiation showed nuclear beta-catenin staining, whereas nonneoplastic Paneth cells consistently showed a normal pattern of membranous beta-catenin staining. A strong topographical correlation was noted between human defensin 5 expression and nuclear beta-catenin expression in conventional adenomas and in conventional dysplastic epithelium of mixed polyps. Paneth cell differentiation is common in early colonic neoplasms that develop via the conventional adenoma-carcinoma carcinogenic pathway. Activation of Apc/beta-catenin/Tcf pathway may play a role in Paneth cell differentiation in human colonic neoplasms. (C) 2009 Elsevier Inc. All rights reserved.