APC mutations are common in adenomas but infrequent in adenocarcinomas of the non-ampullary duodenum
| Autor: | Taiki Hashimoto, Shigeki Sekine, Masashi Kudo, Naoto Gotohda, Ichiro Oda, Takeshi Kuwata, Tomoaki Naka, Motohiro Kojima, Satoru Nonaka, Takaki Yoshikawa, Minoru Esaki, Yasushi Yatabe, Teruhiko Yoshida, Kenichi Ishizu |
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| Rok vydání: | 2021 |
| Předmět: |
Male
medicine.medical_specialty endocrine system diseases Adenoma Adenomatous Polyposis Coli Protein Pyloric Gland Adenoma Adenocarcinoma Gastroenterology Japan Duodenal Neoplasms Internal medicine GNAS complex locus Humans Medicine Aged biology business.industry Not Otherwise Specified Middle Aged medicine.disease digestive system diseases Lynch syndrome stomatognathic diseases medicine.anatomical_structure Duodenum biology.protein Female Duodenal adenocarcinoma business |
| Zdroj: | Journal of Gastroenterology. 56:988-998 |
| ISSN: | 1435-5922 0944-1174 |
| Popis: | Recent studies highlighted the clinicopathological heterogeneity of non-ampullary duodenal adenomas and adenocarcinomas, but the detailed process of the malignant transformation remains unclear. We 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. The 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-truncating APC mutations 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 between GNAS mutations 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. The discrepant APC mutation frequency between adenomas and adenocarcinomas suggests that APC-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. |
| Databáze: | OpenAIRE |
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