title: Could S6K1 immunopositivity be used to distinguish early and advanced stages of endometrioid endometrial adenocarcinoma?
abstract: OBJECTIVE
  To assess whether the immunopositivity of S6K1, a crucial effector of the mTOR signaling pathway, varies between early-stage low-grade and advanced-stage high-grade endometrial endometrioid adenocarcinoma (EEA) as well as to discuss its prognostic significance.
  
  
  METHODS
  A total of 22 normal endometrial tissue samples (Control group) and 41 EEA specimens (Study group) were enrolled in the study, and all the samples underwent immunohistochemical staining for S6 kinase alpha (S6K1). The study group was further evaluated in two subgroups; stage 1A, grade 1 (Group 1) and stage ≥1A, grade 2 or 3 (Group 2). Group 2 patients were considered as a poor prognosis for EEA. The samples were examined by two independent pathologists. Statistical analyses were performed using the Student's t-test for continuous variables, the Chi-square test for categorical variables, and one-way analysis of variance for the comparison of multiple variables.
  
  
  RESULTS
  The immunopositivity rate for all the included EEA patients was 56.1%, whereas none of the 22 normal endometrial tissue samples revealed immunoreactivity for S6K1. The immunopositivity rates were significantly different between Groups 1 and 2 [38.1% (8/21) and 75.0% (15/20), respectively, p=0.039]. When S6K1 positivity was used as a criterion of poor prognosis in EEA, the sensitivity, specificity, positive predictive value, and negative predictive value were calculated to be 62%, 75%, 72%, and 65%, respectively (OR: 4.9 and 95% CI: 1.3-18.7).
  
  
  CONCLUSIONS
  S6K1 was positive in the majority of EEAs and malignancies at an advanced stage. Higher grade disease had a significantly higher rate of S6K1 positivity. S6K1 immunopositivity appears to be a promising method to predict poor prognosis in EEA.
authors.affiliation: Department of Obstetrics and Gynecology, Gülhane Military Medical Academy, Haydarpaşa Training and Research Hospital, İstanbul, Turkey.
authors.forename: İsmet
authors.initials: İ
authors.lastname: Gün
authors.affiliation: Department of Obstetrics and Gynecology, İstanbul Medeniyet University School of Medicine, İstanbul, Turkey.
authors.forename: Özkan
authors.initials: Ö
authors.lastname: Özdamar
authors.affiliation: Department of Pathology, Gülhane Military Medical Academy, Haydarpaşa Training and Research Hospital, İstanbul, Turkey.
authors.forename: Zafer
authors.initials: Z
authors.lastname: Küçükodacı
authors.affiliation: Department of Obstetrics and Gynecology, Gülhane Military Medical Academy, Haydarpaşa Training and Research Hospital, İstanbul, Turkey.
authors.forename: Murat
authors.initials: M
authors.lastname: Muhçu
authors.affiliation: Department of Pathology, Gülhane Military Medical Academy, Haydarpaşa Training and Research Hospital, İstanbul, Turkey.
authors.forename: Dilaver
authors.initials: D
authors.lastname: Demirel
keywords: Endometrioid endometrial adenocarcinoma; P70 ribosomal protein S6 kinase alpha; PI3 K/AKT/mTOR pathway; prognostic indicator