☆ 4.4 Article

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

HUMAN PATHOLOGY (2014)

期刊

HUMAN PATHOLOGY

卷 45, 期 11, 页码 2318-2325

出版社

W B SAUNDERS CO-ELSEVIER INC

DOI: 10.1016/j.humpath.2014.07.020

关键词

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

类别

Pathology

资金

[FEMH-99-D040]
[NTUH100-S1520]

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摘要

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 ten sin 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 ZNF2I7 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. (C) 2014 Elsevier Inc. All rights reserved.

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Clinical analysis and literature review of a case of ovarian clear cell carcinoma with PIK3CA gene mutation: A case report

Abdulkarim Mohamed Farah, Shiyu Gu, Yan Jia

Summary: This study presented a case of OCCC with a PIK3CA mutation, which was successfully managed through careful and complete tumor resection followed by platinum-based chemotherapy. The patient with the PIK3CA gene mutation showed sensitivity to platinum-based chemotherapy, significant decrease in tumor markers, and no recurrence within a year of follow-up, indicating a reasonably good prognosis. Surgery plus platinum-based chemotherapy remains the recommended strategy for OCCC treatment, and genetic testing is advised for predicting the treatment effect.

MEDICINE (2022)