title: Expression and prognostic significance of gastric-specific annexin A10 in diffuse- and intestinal-type gastric carcinoma.
abstract: OBJECTIVE
  Annexin A10 (ANXA10) and its liver-specific short isoform (ANXA10S) had tissue-restricted expression. The downregulation of ANXA10S is correlated with tumor progression and poor prognosis in hepatocellular carcinoma. The aim of the present study was to validate the tissue distribution and explore the role of the ANXA10 protein expression in gastric carcinoma.
  
  
  METHODS
  We examined the ANXA10 protein expression in human and animal tissues and 356 resected primary gastric carcinomas, using specific mouse and rabbit polyclonal antibodies, by immunohistochemical staining.
  
  
  RESULTS
  The ANXA10 protein is a nuclear protein specifically expressed in fetal and adult gastric mucosa and Brunner's gland across species, including humans, minipigs, woodchucks, and mice, and is commonly lost in gastric mucosa with intestinal metaplasia. The ANXA10 protein was expressed in 43.5% (155 cases) of gastric carcinomas; 74.2% (98/132) in the diffuse-type gastric carcinoma (DGC), 73.7% (28/38) in the mixed-type gastric carcinoma, and significantly lower in the intestinal-type gastric carcinoma (IGC) and indeterminate groups, 16.8% (28/167) and 5.3% (1/19), respectively (P<1×10(-8)). IGC with ANXA10 expression was correlated with a higher stage (P=0.049), particularly higher in stage IIIA/IIIB/IV IGC than lower-stage (IA/IB/II) tumors (P=0.005), but was not correlated with age, sex, and nodal status. In contrast, DGC with ANXA10 expression was associated with younger age, female patients, and importantly, lower tumor stage and lymph node metastasis (P=0.007, P=0.065, P=0.024, and P=0.0014, respectively). Moreover, DGC with ANXA10 expression had a better 5-year patient survival (P=0.0048), whereas IGC with ANXA10 expression had a lower 5-year survival (P=0.034).
  
  
  CONCLUSIONS
  The ANXA10 protein expression is a novel marker of gastric differentiation, and is differentially expressed in IGC and DGC, with opposite prognostic significance.
authors.affiliation: Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Su-Hsi
authors.initials: SH
authors.lastname: Lu
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Chen
authors.forename: Chia-Tung
authors.initials: CT
authors.lastname: Shun
authors.forename: Jung-Nien
authors.initials: JN
authors.lastname: Lai
authors.forename: Shian-Yang
authors.initials: SY
authors.lastname: Peng
authors.forename: Po-Lin
authors.initials: PL
authors.lastname: Lai
authors.forename: Hey-Chi
authors.initials: HC
authors.lastname: Hsu
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D017302:Annexins / Q000032:analysis* / Q000235:genetics; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D015153:Blotting, Western; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000737:chemistry; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008392:Marmota; D051379:Mice; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D013552:Swine; D013556:Swine, Miniature; D013624:Taiwan; D013997:Time Factors
chemical_list: C121387:ANXA10 protein, human; D017302:Annexins; C485665:Anxa10 protein, mouse; D014408:Biomarkers, Tumor; D012333:RNA, Messenger