title: Loss of heterozygosity of PTEN (encoding phosphate and tensin homolog) associated with elevated HER2 expression is an adverse prognostic indicator in gastric cancer.
abstract: OBJECTIVE
  PTEN (the encoding phosphate and tensin homolog) is a well-known cancer suppressor gene and its mutation and loss of heterozygosity (LOH) occurs in various types of carcinomas. This study aimed to examine the association between LOH of PTEN and prognosis in HER2-expressing and nonexpressing gastric cancer patients.
  
  
  METHODS
  Fresh-frozen tumor samples of 221 gastric cancer patients with a primary diagnosis of gastric carcinoma were examined for LOH of PTEN. The results were compared with pathological parameters and the HER2 status. To elucidate the role of LOH of PTEN, the activation of the PI3K/AKT pathway was examined immunohistochemically using a phosphorylation-specific antibody.
  
  
  RESULTS
  LOH of PTEN was observed in 20% of the patients (39 of 195 cases). LOH of PTEN was associated with vascular involvement (25 of 39 cases; p = 0.0083), equivocal to positive staining for HER2 (p = 0.0080), and phospho-Akt expression (p = 0.0067). Patients with HER2-expressing gastric cancer with LOH of PTEN had a significantly worse prognosis (p = 0.0050).
  
  
  CONCLUSIONS
  Although HER2 expression itself was not a prognostic factor, the combination of HER2 expression and LOH of PTEN exacerbates the malignant potential of gastric cancer through its proliferative function.
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Zaitsu
authors.forename: Eiji
authors.initials: E
authors.lastname: Oki
authors.forename: Koji
authors.initials: K
authors.lastname: Ando
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ida
authors.forename: Yasue
authors.initials: Y
authors.lastname: Kimura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saeki
authors.forename: Masaru
authors.initials: M
authors.lastname: Morita
authors.forename: Minako
authors.initials: M
authors.lastname: Hirahashi
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Oda
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D051059:PTEN Phosphohydrolase; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human; C494929:PTEN protein, human