title: Decreased expression of 14-3-3σ is predictive of poor prognosis for patients with human uterine papillary serous carcinoma.
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.
authors.affiliation: Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Suzuki
authors.forename: Satoru
authors.initials: S
authors.lastname: Nagase
authors.forename: Kichiya
authors.initials: K
authors.lastname: Suzuki
authors.forename: Etsuko
authors.initials: E
authors.lastname: Oba
authors.forename: Eri
authors.initials: E
authors.lastname: Hiroki
authors.forename: Yukika
authors.initials: Y
authors.lastname: Matsuda
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Akahira
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Nishigori
authors.forename: Takashi
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Takeo
authors.initials: T
authors.lastname: Otsuki
authors.forename: Kousuke
authors.initials: K
authors.lastname: Yoshinaga
authors.forename: Tadao
authors.initials: T
authors.lastname: Takano
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Niikura
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ito
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
authors.forename: Nobuo
authors.initials: N
authors.lastname: Yaegashi
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D018899:CpG Islands / Q000235:genetics; D018283:Cystadenocarcinoma, Papillary / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019175:DNA Methylation / Q000235:genetics; D018572:Disease-Free Survival; D005095:Exoribonucleases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D012008:Recurrence; D014594:Uterine Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014599:Uterus / Q000378:metabolism / Q000473:pathology
chemical_list: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D005095:Exoribonucleases; C413442:SFN protein, human