Decreased expression of 14-3-3σ is predictive of poor prognosis for patients with human uterine papillary serous carcinoma

Fumihiko Suzuki, Satoru Nagase, Kichiya Suzuki, Etsuko Oba, Eri Hiroki, Yukika Matsuda, Jun Ichi Akahira, Hidekazu Nishigori, Takashi Sugiyama, Takeo Otsuki, Kousuke Yoshinaga, Tadao Takano, Hitoshi Niikura, Kiyoshi Ito, Hironobu Sasano, Nobuo Yaegashi

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Uterine papillary serous carcinoma (UPSC) morphologically resembles ovarian serous carcinoma and is categorized as a type II endometrial cancer. UPSC comprises about 10% of all types of endometrial cancer and has an aggressive clinical course and a poor prognosis. The 14-3-3σ gene was originally discovered as a p53-inducible gene; its expression is induced by DNA damage in a p53-dependent manner, which leads to G2 arrest and repair of damaged DNA. Moreover, it has been reported that expression of 14-3-3σ is frequently lost in various types of human cancer, including ovarian cancer. We therefore examined the association between 14-3-3σ expression determined by immunohistochemistry and clinical outcomes of 51 patients with UPSC. UPSC was considered positive for 14-3-3σ when > 30% of tumor cells were stained with a specific antibody. Of these patients, 29 (58.7%) showed positive immunoreactivity for 14-3-3σ and 22 (41.3%) had decreased 14-3-3σ staining. Decreased immunoreactivity for 14-3-3σ was associated with stage (P = 0.001) and lymphovascular space involvement (P = 0.005). Moreover, decreased 14-3-3σ expression was an independent risk factor for reduced overall survival (P = 0.0416) in multivariate analysis. Direct bisulfite sequencing was performed to evaluate the methylation status of the 27 CpG islands in the promoter region and first exon of the 14-3-3σ gene. These CpG islands were hypermethylated in 30% of 14-3-3σ -positive UPSC and 80% of 14-3-3σ -negative UPSC, although the difference was not statistically significant. These findings suggest that decreased expression of immunoreactive 14-3-3σ may be a predictor of poor prognosis in patients with UPSC.

Original languageEnglish
Pages (from-to)193-199
Number of pages7
JournalTohoku Journal of Experimental Medicine
Volume231
Issue number3
DOIs
Publication statusPublished - 2013

Keywords

  • 14-3-3σ
  • Immunohistochemistry
  • Prognostic factor
  • Uterine cancer
  • Uterine papillary serous carcinoma

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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