APC mutations are common in adenomas but infrequent in adenocarcinomas of the non-ampullary duodenum
APC mutations are common in adenomas but infrequent in adenocarcinomas of the non-ampullary duodenum
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APC 突变在腺瘤中常见，但在非壶腹十二指肠腺癌中罕见
DOI：
10.1007/s00535-021-01823-x
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发表时间：
2021
影响因子：
6.3
通讯作者：
Sekine Shigeki
中科院分区：
文献类型：
--
作者：
Ishizu Kenichi;Hashimoto Taiki;Naka Tomoaki;Yatabe Yasushi;Kojima Motohiro;Kuwata Takeshi;Nonaka Satoru;Oda Ichiro;Esaki Minoru;Kudo Masashi;Gotohda Naoto;Yoshida Teruhiko;Yoshikawa Takaki;Sekine Shigeki
近年来的研究强调了非壶腹十二指肠腺瘤和腺癌的临床病理异质性，但其恶变的详细过程尚不清楚。方法分析144例非壶腹十二指肠腺瘤和54例腺癌的免疫组织化学表型、基因改变和错配修复(MMR)状态，以探讨它们之间的组织发生关系。其中肠型腺瘤( )12 4例，幽门腺瘤( )10例，胃型腺瘤( )9例，凹陷型腺瘤( )1例。APC基因突变在腺瘤中的发生率很高(85%)，其中肠型腺瘤的发生率最高(89%)，而腺癌的发生率很低(9%；P= 2.1 × 10-23)。在腺瘤中观察到表型标记物的表达与遗传改变密切相关，而在腺癌中未观察到，排除了GNAS突变与MUC5AC表达之间的共同联系。腺癌MMR缺陷率(20%)明显高于腺瘤(1%；P= 2.6 × 10-6)。在Lynch综合征患者中，发生了一个MMR缺陷性腺瘤和三个MMR缺陷性腺癌。结论腺瘤和腺癌之间APC突变频率不同，表明APC突变的腺瘤在非壶腹十二指肠腺瘤中占绝大多数，不易发生恶变。非壶腹十二指肠腺癌经常表现出MMR缺陷，应该接受MMR测试以确定适当的临床处理，包括鉴定患有林奇综合征的患者。
BackgroundRecent studies highlighted the clinicopathological heterogeneity of non-ampullary duodenal adenomas and adenocarcinomas, but the detailed process of the malignant transformation remains unclear.MethodsWe analyzed 144 adenomas and 54 adenocarcinomas of the non-ampullary duodenum for immunohistochemical phenotypes, genetic alterations, and mismatch repair (MMR) status to probe their histogenetic relationship.ResultsThe median ages of patients with adenoma and adenocarcinoma were the same (66 years). Adenomas were histologically classified as intestinal-type adenoma (n= 124), pyloric gland adenoma (PGA,n= 10), gastric-type adenoma, not otherwise specified (n= 9), and foveolar-type adenoma (n= 1). Protein-truncatingAPCmutations were highly frequent in adenomas (85%), with the highest prevalence in intestinal-type adenomas (89%), but rare in adenocarcinomas (9%;P= 2.1 × 10–23). Close associations between phenotypic marker expression and genetic alterations were observed in adenomas, but not in adenocarcinomas, excluding the common association betweenGNASmutations and MUC5AC expression. MMR deficiency was more frequent in adenocarcinomas (20%) than in adenomas (1%;P= 2.6 × 10–6). One MMR-deficient adenoma and three MMR-deficient adenocarcinomas occurred in patients with Lynch syndrome. Additionally, three other patients with an MMR-deficient adenocarcinoma fulfilled the revised Bethesda criteria.ConclusionThe discrepantAPCmutation frequency between adenomas and adenocarcinomas suggests thatAPC-mutated adenomas, which constitute the large majority of non-ampullary duodenal adenomas, are less prone to malignant transformation. Non-ampullary duodenal adenocarcinomas frequently exhibit MMR deficiency and should be subject to MMR testing to determine appropriate clinical management, including the identification of patients with Lynch syndrome.
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<1 cm 结直肠腺瘤绒毛成分和高度不典型增生的重现性：对内镜监测的意义
影响因子：
5.6
作者：
Dipti Mahajan;E. Downs‐Kelly;Xiuli Liu;R. Pai;Deepa T. Patil;L. Rybicki;A. Bennett;T. Plesec;O. Cummings;D. Rex;J. Goldblum
通讯作者：
J. Goldblum
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DOI：
10.1097/pas.0b013e3181723679
发表时间：
2008
期刊：
The American Journal of Surgical Pathology
影响因子：
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作者：
Patrick L. Wagner;Yao;R. Yantiss
通讯作者：
R. Yantiss
影响因子：
29.4
作者：
Jenkins, Mark A.;Hayashi, Shinichi;Jass, Jeremy R.
通讯作者：
Jass, Jeremy R.
影响因子：
12.6
作者：
Latchford, Andrew R.;Neale, Kay F.;Clark, Susan K.
通讯作者：
Clark, Susan K.
影响因子：
6.4
作者：
Hijikata, Kazunori;Nemoto, Tetsuo;Shibuya, Kazutoshi
通讯作者：
Shibuya, Kazutoshi