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恒河猴(猕猴)大肠腺癌的免疫组织化学特征

Immunohistochemical Characterization of Large Intestinal Adenocarcinoma in the Rhesus Macaque (Macaca mulatta).

作者信息

Harbison C E, Taheri F, Knight H, Miller A D

机构信息

New England Primate Research Center, Division of Comparative Pathology, Harvard Medical School, Southborough, MA, USA.

Abbvie Bioresearch Center, Worcester, MA, USA.

出版信息

Vet Pathol. 2015 Jul;52(4):732-40. doi: 10.1177/0300985814556188. Epub 2014 Nov 3.

Abstract

In rhesus macaques, adenocarcinomas of either the ileocecal junction or colon are common spontaneous tumors in aging populations. The macaque tumors have similar gross and histologic characteristics compared with their human counterpart, but little is known regarding the immunohistochemical expression of proteins that are commonly implicated in the pathogenesis of these tumors in humans. We performed a retrospective review of 22 cases of large intestinal carcinoma in the rhesus macaque and evaluated the expression pattern of a panel of potentially prognostically significant proteins identified from human studies. Histologic characteristics of the tumors included abundant mucin deposition, transmural spread, and lymphatic invasion. All rhesus adenocarcinomas displayed altered expression of 1 or more of CD10, β-catenin, sirtuin 1, cytokeratin 17, and p53 compared with age-matched controls. Zymographic analysis of active matrix metalloproteinases 2 and 9 in the serum from 5 animals failed to reveal statistically significant differences between adenocarcinoma cases and controls. Based on the data presented herein, large intestinal carcinomas in the macaque share many histomorphologic and immunohistochemical similarities to large intestinal tumors in humans. Further validation of this animal model is considered important for the development of novel therapeutics and a better understanding of the pathogenesis.

摘要

在恒河猴中,回盲部或结肠腺癌是老龄群体中常见的自发性肿瘤。与人类同类肿瘤相比,猕猴肿瘤具有相似的大体和组织学特征,但对于人类这些肿瘤发病机制中常见的蛋白质的免疫组化表达情况知之甚少。我们对22例恒河猴大肠腺癌病例进行了回顾性研究,并评估了一组从人类研究中确定的具有潜在预后意义的蛋白质的表达模式。肿瘤的组织学特征包括大量黏液沉积、透壁扩散和淋巴浸润。与年龄匹配的对照组相比,所有恒河猴腺癌均显示CD10、β-连环蛋白、沉默调节蛋白1、细胞角蛋白17和p53中的1种或更多种表达改变。对5只动物血清中活性基质金属蛋白酶2和9进行酶谱分析,未发现腺癌病例与对照组之间存在统计学上的显著差异。基于本文提供的数据,猕猴的大肠腺癌与人类大肠肿瘤在许多组织形态学和免疫组化方面具有相似性。进一步验证这种动物模型对于开发新疗法和更好地理解发病机制具有重要意义。

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