title: Tubular adenoma and intramucosal intestinal-type adenocarcinoma of the stomach: what are the pathobiological differences?
abstract: BACKGROUND
  The concept of human early gastric cancer has discrepancies among pathologists worldwide. Recently, a novel morphological classification of gastrointestinal intramucosal neoplasias was proposed and conceptual differences have gradually decreased. However, there are few studies on the differences of pathobiological properties among the intraepithelial neoplasms. The aim of the present study was to clarify the clinicopathological significance of gastric intramucosal tumors from the pathobiological viewpoint.
  
  
  METHODS
  This study analyzed 70 tubular adenomas (TAs) with mild or moderate atypia and 52 intramucosal intestinal-type adenocarcinomas (IMACs) of the stomach from the viewpoint of the apoptotic index (AI), Ki-67 labeling index (KI), and intratumoral microvessel density (IMVD), using immunohistochemistry and the terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick-end labeling (TUNEL) method. We also examined the expression of P53 and thymidine phosphorylase (dThdPase).
  
  
  RESULTS
  The mean AI was significantly higher and the mean KI and IMVD were significantly lower in the TAs than in the IMACs (P < 0.05, P < 0.001, and P < 0.01, respectively). AI and IMVD showed a negative correlation in TAs and IMACs (TAs; P = 0.015; r = 0.28; IMACs; P = 0.006; r = 0.41). dThdPase and nuclear P53 expression were significantly higher in the IMACs than in the TAs (P < 0.05, P < 0.01). Mean IMVD was significantly higher in dThdPase-positive tumors than in the negative ones (P < 0.01, P < 0.01) in both TAs and IMACs.
  
  
  CONCLUSIONS
  IMACs possess higher proliferative activity of tumor cells, with a vascular-rich microenvironment, than TAs. This might reflect the pathobiological differences between gastric IMACs and TAs, and could also provide useful information on indications for gastric endoscopic mucosal resection for IMACs as has been recommended by the Japanese Gastric Cancer Association.
authors.affiliation: Division of Organ Pathology, Department of Microbiology and Pathology, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Kase
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Osaki
authors.forename: Soichiro
authors.initials: S
authors.lastname: Honjo
authors.forename: Hironobu
authors.initials: H
authors.lastname: Adachi
authors.forename: Hisao
authors.initials: H
authors.lastname: Ito
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D000236:Adenoma / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D017209:Apoptosis / Q000502:physiology; D001485:Basement Membrane / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D003937:Diagnosis, Differential; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D020397:Goblet Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D007564:Japan; D019394:Ki-67 Antigen / Q000378:metabolism; D013223:Statistics as Topic; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D013939:Thymidine Phosphorylase / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
chemical_list: D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D013939:Thymidine Phosphorylase