title: Carcinogenesis of gastric endocrine cell carcinoma: analysis of histopathology and p53 gene alteration.
abstract: BACKGROUND
  Endocrine cell carcinoma of the stomach is characterized by endocrine differentiation and aggressive biological behavior, and is frequently accompanied by an adenocarcinoma component. Because the carcinogenic parthway and genetic alterations remain unclear, we investigated the histogenesis of the tumor by histopathological and p53 gene analysis.
  
  
  METHODS
  The materials were 68 gastric endocrine cell carcinomas and 30 carcinoid tumors, which were resected from 93 Japanese patients for histopathological and immunohistochemical investigation. We also analyzed the concordance of p53 mutational status between the associated adenocarcinoma and endocrine cell carcinoma components, using microdissection and direct sequencing techniques.
  
  
  RESULTS
  An adenocarcinoma component was associated with 70.6% (48/68) of endocrine cell carcinomas, of which 42 (87.5%) were of well- to moderately differentiated type, while 36 of these 42 (85.7%) demonstrated histological continuity with the endocrine cell carcinoma components. Overexpression of p53 protein was observed in 58.8% (20/34) of cases. Common p53 mutational status between the two components was revealed in 73.3% (11/15) of cases analyzed. In contrast, carcinoid tumors did not exhibit p53 protein overexpression (0/15) or gene mutation (0/5).
  
  
  CONCLUSIONS
  These data suggest that gastric endocrine cell carcinomas predominantly arise from endocrine precursor cell clones occurring in preceding adenocarcinoma components (particularly the differentiated type), transforming into endocrine cell carcinoma during rapid clonal expansion under the influence of p53 gene alteration. Endocrine cell carcinoma of the stomach is characterized by endocrine differentiation and aggressive biological behavior, and is frequently accompanied by an adenocarcinoma component. Because the carcinogenic pathway and genetic alterations remain unclear, we investigated the histogenesis of this tumor by histopathological and p53 gene analysis.
authors.affiliation: Division of Molecular and Functional Pathology, Department of Cellular Function, Niigata University Graduate School of Medical and Dental Sciences, 1 Asahimachi-dori, 951-8510, Niigata, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Nishikura
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Watanabe
authors.forename: Mitsuya
authors.initials: M
authors.lastname: Iwafuchi
authors.forename: Takato
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Kazuko
authors.initials: K
authors.lastname: Kojima
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ajioka
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000503:physiopathology*; D000368:Aged; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic; D004701:Endocrine Gland Neoplasms / Q000235:genetics* / Q000503:physiopathology*; D019858:Enteroendocrine Cells / Q000473:pathology*; D005260:Female; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D013274:Stomach Neoplasms / Q000235:genetics* / Q000503:physiopathology*