title: Clonality analysis of neuroendocrine cells in gastric adenocarcinoma.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  NE and the gastric adenocarcinoma cells may mainly derive from the same stem cells, but the remaining cases showing different origin needs further investigation.
authors: Institute of Pathology and Forensic Medicine, Zhejiang University, Hangzhou 310058, Zhejiang Province, China.
authors: Ling-Ling
authors: LL
authors: Wang
authors: Gen-You
authors: GY
authors: Yao
authors: Zhong-Sheng
authors: ZS
authors: Zhao
authors: Xiao-Li
authors: XL
authors: Wei
authors: Ru-Jun
authors: RJ
authors: Xu
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics*; D002454:Cell Differentiation; D019070:Cell Lineage; D016009:Chi-Square Distribution; D002999:Clone Cells; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D019656:Loss of Heterozygosity; D008207:Lymphatic Metastasis; D053842:Microsatellite Instability; D009154:Mutation; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D055099:Neuroendocrine Cells / Q000737:chemistry* / Q000473:pathology; D010641:Phenotype; D011379:Prognosis; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: Clonal analysis; Gastric adenocarcinoma; Neuroendocrine cells; Neuroendocrine differentiation
references: Cancer. 1998 Aug 1;83(3):435-44
references: 9690535
references: Ann N Y Acad Sci. 2000 Jun;910:121-37; discussion 137-9
references: 10911910
references: Fam Cancer. 2009;8(3):215-20
references: 19152022
references: Tumori. 2003 Jan-Feb;89(1):49-53
references: 12729362
references: Arch Pathol Lab Med. 2002 Apr;126(4):437-41
references: 11900568
references: Cancer. 1996 Apr 15;77(8 Suppl):1620-7
references: 8608553
references: Virchows Arch. 2002 Jan;440(1):85-93
references: 11942581
references: Eur Urol. 2004 May;45(5):586-92; discussion 592
references: 15082200
references: World J Gastroenterol. 2006 Jan 21;12(3):354-62
references: 16489633
references: Gastric Cancer. 2003;6(4):203-9
references: 14716513
references: Blood. 1994 Oct 15;84(8):2391-411
references: 7919359
references: Hum Pathol. 2005 Jul;36(7):732-40
references: 16084941
references: Pathol Oncol Res. 2004;10(1):47-51
references: 15029262
references: Cancer Res. 1993 Jun 1;53(11):2614-7
references: 8495424
references: World J Gastroenterol. 2003 Apr;9(4):858-61
references: 12679948
references: Gut. 2001 Jun;48(6):853-6
references: 11358908
references: Chin Med J (Engl). 2004 Oct;117(10):1536-40
references: 15498379
references: Gan To Kagaku Ryoho. 2008 Feb;35(2):343-9
references: 18281780
references: Virchows Arch. 1995;426(4):339-44
references: 7599785
references: Urology. 2003 Nov;62(5 Suppl 1):11-20
references: 14607213
references: Cancer Res. 1993 Nov 1;53(21):5087-9
references: 8221640
references: Science. 1991 Jul 5;253(5015):49-53
references: 1905840
references: Ann Oncol. 2006 Jun;17 Suppl 7:vii97-102
references: 16760303
references: World J Gastroenterol. 2008 May 28;14(20):3269-72
references: 18506939
references: World J Gastroenterol. 2009 Mar 21;15(11):1381-7
references: 19294769