Chromosome 20q13.2 ZNF217 locus amplification correlates with decreased E-cadherin expression in ovarian clear cell carcinoma with PI3K-Akt pathway alterations
Journal
Human Pathology
Journal Volume
45
Journal Issue
11
Pages
2318-2325
Date Issued
2014
Author(s)
Abstract
This study aims to evaluate the relationships between chromosome 20q13.2 zinc finger protein 217 (ZNF217) locus amplification, ZNF217 expression, E-cadherin expression, and PI3K-Akt pathway alterations (activating PIK3CA mutations or loss of phosphatase and tensin homolog [PTEN] expression), and whether these molecular alterations can predict the clinical survival data in ovarian clear cell carcinoma (OCCC) patients. Samples and clinical data of 72 OCCC patients were collected. Chromosome 20q13.2 ZNF217 locus amplification was detected by fluorescence in situ hybridization. ZNF217, E-cadherin and PTEN expression were assessed using immunohistochemical stain. PIK3CA mutation was identified by PCR-amplified gene sequencing. Cox proportional hazard regression model was used to estimate the adjusted hazard ratios of survival. Chromosome 20q13.2 ZNF217 locus amplification was detected in 31% (22/72) of cases, and ZNF217 expression was increased in 40% (27/68) of cases. E-cadherin and PTEN expressions were decreased or lost in 44% (32/72) and 14% (10/72) of cases, respectively. Activating PIK3CA mutations were present in 35% (25/72) of cases. Thirty-three OCCC patients (46%) showed activating PI3K-Akt pathway alterations. Chromosome 20q13.2 ZNF217 locus amplification was significantly associated with decreased E-cadherin expression (P =.001). In contrast, ZNF217 expression was not related to ZNF217 amplification or E-cadherin expression. In OCCC patients with activating PI3k-Akt pathway, decreased E-cadherin expression (P =.033) and advanced Federation of Gynecology and Obstetrics stage (P =.014) predicted shorter overall survival. Two conclusions were raised in our study. First, ZNF217 plays a role in down-regulating E-cadherin expression and is a potential therapeutic target for OCCC patients. Second, E-cadherin expression is a prognostic marker for OCCC patients with activating PI3K-Akt pathway. ? 2014 Elsevier Inc.
SDGs
Other Subjects
phosphatidylinositol 3 kinase; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; phosphoinositide 3 kinase catalytic subunit alpha; protein kinase B; unclassified drug; uvomorulin; zinc finger protein; zinc finger protein 217; cadherin; phosphatidylinositol 3 kinase; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; protein kinase B; PTEN protein, human; adult; Article; cancer prognosis; cancer size; cancer survival; chromosome; chromosome mutation; clear cell carcinoma; down regulation; enzyme activation; female; fluorescence in situ hybridization; gene amplification; gene expression; gene identification; gene locus; gene sequence; genetic association; human; human tissue; immunohistochemistry; major clinical study; ovary carcinoma; overall survival; polymerase chain reaction; signal transduction; somatic mutation; adenocarcinoma; chromosome 20; genetics; metabolism; middle aged; ovary tumor; pathology; phosphorylation; prognosis; Adenocarcinoma, Clear Cell; Cadherins; Chromosomes, Human, Pair 20; Female; Gene Amplification; Humans; Middle Aged; Ovarian Neoplasms; Phosphatidylinositol 3-Kinases; Phosphorylation; Prognosis; Proto-Oncogene Proteins c-akt; PTEN Phosphohydrolase; Signal Transduction
Publisher
W.B. Saunders
Type
journal article