title: Loss of expression of tumor suppressor p16(INK4) protein in human primary gastric cancer is related to the grade of differentiation.
abstract: BACKGROUND
  Recent research has revealed a rapid increase in the number of alterations underlying oncogenesis and the proteins which regulate the cell cycle. p16 is a cell cycle regulatory protein acting as a cyclin-dependent kinase inhibitor (CDKI). Because of its antiproliferative effect, p16 has been suggested to be a tumor suppressor gene. Deletions, mutations and functional inactivation of p16 occur with a frequency second only to p53 in most human malignancies.
  
  
  OBJECTIVE
  to evaluate the p16 protein expression in primary gastric cancer in order to understand the possible differences in relation to histotype and grade of tumors.
  
  
  METHODS
  Immunohistochemical expression of p16 was investigated in matched normal and cancerous tissues from 70 patients with gastric cancer (52 intestinal and 18 diffuse type).
  
  
  RESULTS
  In non-cancerous gastric tissues the immunostaining of p16 was weak and limited to antral glands. In gastric cancer tissues, the enhanced immunoreactivity of p16 was not significantly different in intestinal and diffuse type of gastric cancer. However, the intensity of immunostaining was inversely related to the grade of differentiation of these tumours.
  
  
  CONCLUSIONS
  The overexpression of p16 seems to be a common event in the development of both intestinal and diffuse type of gastric cancer and it is likely that it may be driven by features of the neoplastic state. Likewise, the absence of p16 in the lowest grade of differentiation may reflect increased selection pressure and clonal expansion of the cells with a more aggressive phenotype.
authors.affiliation: Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Alba
authors.initials: A
authors.lastname: Rocco
authors.forename: Laslo
authors.initials: L
authors.lastname: Schandl
authors.forename: Gerardo
authors.initials: G
authors.lastname: Nardone
authors.forename: Zolt
authors.initials: Z
authors.lastname: Tulassay
authors.forename: Stefania
authors.initials: S
authors.lastname: Staibano
authors.forename: Peter
authors.initials: P
authors.lastname: Malfertheiner
authors.forename: Matthias P A
authors.initials: MP
authors.lastname: Ebert
mesh_terms: D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis* / Q000235:genetics; D019942:Genes, p16; D006801:Humans; D007150:Immunohistochemistry; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16