Brief Article
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World J Gastroenterol. Aug 28, 2013; 19(32): 5340-5346
Published online Aug 28, 2013. doi: 10.3748/wjg.v19.i32.5340
Clonality analysis of neuroendocrine cells in gastric adenocarcinoma
Ling-Ling Wang, Gen-You Yao, Zhong-Sheng Zhao, Xiao-Li Wei, Ru-Jun Xu
Ling-Ling Wang, Institute of Pathology and Forensic Medicine, Zhejiang University, Hangzhou 310058, Zhejiang Province, China
Ling-Ling Wang, Pathology Department, Hangzhou First People’s Hospital, Hangzhou 310006, Zhejiang Province, China
Gen-You Yao, Xiao-Li Wei, Institute of Pathology and Forensic Medicine, Zhejiang University, Hangzhou 310058, Zhejiang Province, China
Zhong-Sheng Zhao, Zhejiang Provincial People’s Hospital, Hangzhou 310014, Zhejiang Province, China
Ru-Jun Xu, Hangzhou First People’s Hospital, Hangzhou 310006, Zhejiang Province, China
Author contributions: Wang LL and Yao GY designed research; Wang LL performed research; Zhao ZS, Wei XL and Xu RJ contributed new reagents or analytic tools; Wang LL and Wei XL analyzed data; Wang LL wrote the paper.
Supported by The Natural Science Foundation of Zhejiang Province, China, No. Y2110133; the Zhejiang Provincial Medical Science Research Foundation, No. 2010KYA060
Correspondence to: Gen-You Yao, Professor of Medicine, Institute of Pathology and Forensic Medicine, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, Zhejiang Province, China. yaogy@zju.edu.cn
Telephone: +86-571-87065701 Fax: +86-571-87914771
Received: March 24, 2013
Revised: June 13, 2013
Accepted: July 4, 2013
Published online: August 28, 2013
Abstract

AIM: To achieve a better understanding of the origination of neuroendocrine (NE) cells in gastric adenocarcinoma.

METHODS: In this study, 120 cases of gastric adenocarcinoma were obtained. First, frozen section-immunohistochemistrical samples were selected from a large quantity of neuroendocrine cells. Second, laser capture microdissection was used to get target cells from gastric adenocarcinoma and whole genome amplification was applied to get a large quantity of DNA for further study. Third, genome-wide microsatellite abnormalities [microsatellite instability (MSI), loss of heterozygosity (LOH)] and p53 mutation were detected by polymerase chain reaction (PCR)-single-strand conformation polymer- phism-silver staining and PCR-sequencing in order to identify the clonality of NE cells.

RESULTS: The total incidence rate of MSI was 27.4%, while LOH was 17.9%. Ten cases had a highest concordance for the two types of cells. The other samples had similar microsatellite changes, except for cases 7 and 10. Concordant p53 mutations exhibited in sample 4, 14, 21 and 27, and there were different mutations between two kinds of cells in case 7. In case 17, mutation took place only in adenocarcinoma cells. p53 mutation was closely related with degree of differentiation, tumor-node-metastasis stage, vessel invasion and lymph node metastasis. In brief, NE and adenocarcinoma cells showed the same MSI, LOH or p53 mutation in most cases (27/30). In the other three cases, different MSI, LOH or p53 mutation occurred.

CONCLUSION: NE and the gastric adenocarcinoma cells may mainly derive from the same stem cells, but the remaining cases showing different origin needs further investigation.

Keywords: Neuroendocrine differentiation, Clonal analysis, Gastric adenocarcinoma, Neuroendocrine cells

Core tip: There have been only a few studies of neuroendocrine differentiation (NED) in gastric adenocarcinoma. Therefore, we studied the clonality of neuroendocrine (NE) cells in gastric adenocarcinoma using laser capture microdissection, microsatellite instability (MSI), loss of heterozygosity (LOH) and p53 mutation to evaluate the clonality of NED. NE and adenocarcinoma cells showed the same MSI, LOH or p53 mutation in most cases (27/30), they may originate from the same stem cells, but the remaining three cases showed different origins, which warrants further research.