Decreased Expression of 14-3-3 sigma Is Predictive of Poor Prognosis for Patients with Human Uterine Papillary Serous Carcinoma

作者：Suzuki Fumihiko; Nagase Satoru^*; Suzuki Kichiya; Oba Etsuko; Hiroki Eri; Matsuda Yukika; Akahira Jun ichi; Nishigori Hidekazu; Sugiyama Takashi; Otsuki Takeo; Yoshinaga Kousuke; Takano Tadao; Niikura Hitoshi; Ito Kiyoshi; Sasano Hironobu; Yaegashi Nobuo

来源：Tohoku Journal of Experimental Medicine, 2013, 231(3): 193-199.

DOI：10.1620/tjem.231.193

• 14-3-3 sigma
• immunohistochemistry
• prognostic factor
• uterine cancer
• uterine papillary serous carcinoma

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 14-3-3 sigma 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 14-3-3 sigma is frequently lost in various types of human cancer, including ovarian cancer. We therefore examined the association between 14-3-3 sigma expression determined by immunohistochemistry and clinical outcomes of 51 patients with UPSC. UPSC was considered positive for 14-3-3 sigma when > 30% of tumor cells were stained with a specific antibody. Of these patients, 29 (58.7%) showed positive immunoreactivity for 14-3-3 sigma and 22 (41.3%) had decreased 14-3-3 sigma staining. Decreased immunoreactivity for 14-3-3 sigma was associated with stage (P = 0.001) and lymphovascular space involvement (P = 0.005). Moreover, decreased 14-3-3 sigma 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 14-3-3 sigma gene. These CpG islands were hypermethylated in 30% of 14-3-3 sigma-positive UPSC and 80% of 14-3-3 sigma-negative UPSC, although the difference was not statistically significant. These findings suggest that decreased expression of immunoreactive 14-3-3 sigma may be a predictor of poor prognosis in patients with UPSC.

• 出版日期2013-11