Chromosome 20q13.2 ZNF217 locus amplification correlates with decreased E-cadherin expression in ovarian clear cell carcinoma with PI3K-Akt pathway alterations

Hsien-Neng Huang; Wen-Chih Huang; Ching-Hung Lin; Ying-Cheng Chiang; Hsin-Ying Huang; Kuan-Ting Kuo

doi:10.1016/j.humpath.2014.07.020

Chromosome 20q13.2 ZNF217 locus amplification correlates with decreased E-cadherin expression in ovarian clear cell carcinoma with PI3K-Akt pathway alterations

Hum Pathol. 2014 Nov;45(11):2318-25. doi: 10.1016/j.humpath.2014.07.020. Epub 2014 Aug 16.

Authors

Hsien-Neng Huang¹, Wen-Chih Huang², Ching-Hung Lin³, Ying-Cheng Chiang⁴, Hsin-Ying Huang⁵, Kuan-Ting Kuo⁶

Affiliations

¹ Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan, 10002; Department of Pathology, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan, 30059.
² Department of Anatomic Pathology, Far Eastern Memorial Hospital, Taipei, Taiwan, 22060.
³ Department of Oncology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan, 10002.
⁴ Department of Obstetrics and Gynecology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan, 10002.
⁵ Department of Mathematics Education, National Chengchi University, Taipei, Taiwan, 11605.
⁶ Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan, 10002; Department of Pathology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan, 10002. Electronic address: pathologykimo@gmail.com.

PMID: 25281027
DOI: 10.1016/j.humpath.2014.07.020

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.

Keywords: E-cadherin; Ovarian clear cell carcinoma; PIK3CA; PTEN; Prognosis; ZNF217.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma, Clear Cell / genetics
Adenocarcinoma, Clear Cell / metabolism*
Adenocarcinoma, Clear Cell / pathology
Cadherins / metabolism*
Chromosomes, Human, Pair 20
Female
Gene Amplification*
Humans
Middle Aged
Ovarian Neoplasms / genetics
Ovarian Neoplasms / metabolism*
Ovarian Neoplasms / pathology
PTEN Phosphohydrolase / metabolism
Phosphatidylinositol 3-Kinases / metabolism*
Phosphorylation
Prognosis
Proto-Oncogene Proteins c-akt / metabolism*
Signal Transduction / genetics

Substances

Cadherins
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins c-akt
PTEN Phosphohydrolase
PTEN protein, human