Immunohistochemical and Molecular Features of Sporadic and FAP-associated Duodenal Adenomas of the Ampullary and Nonampullary Mucosa
Immunohistochemical and Molecular Features of Sporadic and FAP-associated Duodenal Adenomas of the Ampullary and Nonampullary Mucosa
复制标题
壶腹和非壶腹粘膜散发性和 FAP 相关十二指肠腺瘤的免疫组织化学和分子特征
DOI：
10.1097/pas.0b013e3181723679
复制
发表时间：
2008
期刊：
影响因子：
--
通讯作者：
R. Yantiss
中科院分区：
文献类型：
--
作者：
Patrick L. Wagner;Yao;R. Yantiss
十二指肠腺瘤的发病机制尚不清楚。许多文献涉及壶腹腺瘤和家族性腺瘤性息肉病（FAP）。在本研究中，我们评估了发生在壶腹远端的一系列散发性十二指肠腺瘤（n=22）的分子特征，并将其与散发性壶腹腺瘤（n=9）和fap相关息肉（n=12）的特征进行了比较。结合免疫组织化学研究[细胞角蛋白7和20，E-cadherin, β-catenin, p53, MLH-1, MSH-2， MSH-6和o6 -甲基鸟嘌呤甲基转移酶（MGMT）]， DNA测序[β-catenin，腺瘤性息肉病大肠（APC）， p53， KRAS和BRAF]，以及基于聚合酶链反应的微卫星不稳定性测定；我们评估了每个Wnt信号和丝裂原激活的蛋白激酶途径以及DNA修复机制的异常情况。Wnt信号通路异常在散发、非壶腹腺瘤（82%）和壶腹腺瘤（77%）中发生率相当，通常反映核β-catenin免疫染色（分别为64%和44%）和APC而不是β-catenin突变。KRAS突变在散发性、非壶腹性腺瘤（18%）和fap相关性腺瘤（9%）中少见；中度多发于壶腹腺瘤（44%）；没有一例携带BRAF突变。仅有4例（13%）散发性腺瘤显示核p53染色，但外显子5 ~ 8未检测到p53突变。o6 -甲基鸟嘌呤甲基转移酶免疫染色缺失在1例散发性非壶腹腺瘤中发现，任何组的息肉均未出现MLH-1、MSH-2或MSH-6染色缺失或高频微卫星不稳定性。我们的结论是，散发性和fap相关腺瘤表现出相似的分子特征，无论其解剖位置如何。与结直肠腺瘤相似，它们含有APC和KRAS突变；但BRAF突变、p53改变和DNA错配修复异常是罕见的。
The pathogenesis of duodenal adenomas is not well elucidated. Much of the literature pertains to ampullary adenomas and those associated with familial adenomatous polyposis (FAP). In this study, we evaluated the molecular features of a series of sporadic duodenal adenomas (n=22) that developed distal to the ampulla, and compared them with the features of sporadic ampullary adenomas (n=9) and FAP-related polyps (n=12). Using a combination of immunohistochemical studies [cytokeratins 7 and 20, E-cadherin, β-catenin, p53, MLH-1, MSH-2, MSH-6, and O6-methylguanine methyltransferase (MGMT)], DNA sequencing [β-catenin, adenomatous polyposis coli (APC), p53, KRAS, and BRAF], and a polymerase chain reaction-based microsatellite instability assay; we assessed each case for abnormalities in the Wnt signaling and mitogen-activated protein kinase pathways and DNA repair mechanisms. Wnt signaling pathway abnormalities occurred in sporadic, nonampullary (82%), and ampullary (77%) adenomas at comparable rates, usually reflecting nuclear β-catenin immunostaining (64% and 44%, respectively), and APC rather than β-catenin, mutations. KRAS mutations were infrequent in sporadic, nonampullary adenomas (18%), and FAP-related adenomas (9%); moderately frequent in ampullary adenomas (44%); and none of the cases harbored BRAF mutations. Only 4 (13%) sporadic adenomas showed nuclear p53 staining, but no p53 mutations were detected in exons 5 to 8. Loss of O6-methylguanine methyltransferase immunostaining was identified in 1 sporadic, nonampullary adenoma, and none of the polyps in any group showed loss of MLH-1, MSH-2, or MSH-6 staining, or high-frequency microsatellite instability. We conclude that sporadic and FAP-related adenomas show similar molecular features, regardless of their anatomic location. Similar to colorectal adenomas, they harbor APC and KRAS mutations; but BRAF mutations, p53 alterations, and DNA mismatch repair abnormalities are rare.
影响因子：
3.3
作者：
Arber, N;Gammon, MD;Weinstein, IB
通讯作者：
Weinstein, IB
影响因子：
6
作者：
Loukola, A;Salovaara, R;Aaltonen, LA
通讯作者：
Aaltonen, LA