Loss of heterozygosity of PTEN (Encoding phosphate and tensin homolog) associated with elevated HER2 expression is an adverse prognostic indicator in gastric cancer

Yoko Zaitsu, Eiji Oki, Koji Ando, Satoshi Ida, Yasue Kimura, Hiroshi Saeki, Masaru Morita, Minako Hirahashi, Yoshinao Oda, Yoshihiko Maehara

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)189-194
Number of pages6
JournalOncology (Switzerland)
Volume88
Issue number3
DOIs
Publication statusPublished - Mar 6 2015

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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