CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Editors: Michael Cibull, MD, professor emeritus, University of Kentucky College of Medicine, Lexington; Rouzan Karabakhtsian, MD, attending pathologist, Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; Thomas Cibull, MD, dermatopathologist, Evanston Hospital, NorthShore University HealthSystem, Evanston, Ill.; and Rachel Stewart, DO, resident physician, Department of Pathology and Laboratory Medicine, University of Kentucky.
Alteration of ARID1A gene, PI3K-Akt pathway, and ZNF217 gene in ovarian clear cell carcinoma
AT-rich interactive domain 1A (ARID1A) is a subunit of switch/sucrose nonfermentable (SWI/SNF) complex. Recently, alterations of the ARID1A gene, phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) pathway, and zinc-finger protein 217 (ZNF217) gene have been identified as frequent molecular genetic changes in ovarian clear cell carcinoma. The relationships between these events have not been studied and integrated in the same cohort. The authors conducted a study to determine the correlation between these events and other clinicopathological factors, including the prognostic impact of these factors. They collected 68 ovarian clear cell carcinoma cases and subjected them to immunohistochemistry testing for ARID1A, SMARCA2, SMARCA4, SMARCB1 and phosphatase and tensin homolog (PTEN), mutation analysis for the phosphatidylinositol-4, 5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) gene, and fluorescence in situ hybridization for ZNF217 amplification. They then analyzed the correlations between ARID1A expression, P13K-Akt pathway, ZNF217 amplification, and other clinicopathological factors. Loss of ARID1A expression was present in 35 (52 percent) cases, and loss of SMARCA2 expression occurred in one case. SMARCA4 and SMARCB1 expression were preserved in all cases. PIK3CA mutations were present in 23 (34 percent) cases, and loss of PTEN expression occurred in eight (12 percent) cases. Alterations in the PI3K-Akt pathway (PIK3CA mutations or loss of PTEN expression) were found in 42 (62 percent) cases. ZNF217 amplification was detected in 21 (31 percent) cases. Loss of ARID1A expression was significantly related to younger patient age (P=0.048), PI3K-Akt pathway activation (P=0.046), and ZNF217 amplification (P=0.028). All of the clinicopathological factors were not prognostic factors for ovarian clear cell carcinoma after multivariate analysis, except International Federation of Gynecology and Obstetrics staging (P=0.001). The results of the study showed that loss of ARID1A expression usually coexists with PI3K-Akt pathway activation or ZNF217 amplification, or both. Synergic effects of loss of ARID1A and PI3K-Akt pathway activation, as well as ZNF217 amplification, may be related to the development of ovarian clear cell carcinoma.
Huang HN, Lin MC, Huang WC, et al. Loss of ARID1A expression and its relationship with PI3K-Akt pathway alterations and ZNF217 amplification in ovarian clear cell carcinoma. Mod Pathol. 2014;27:983–990.
Correspondence: Dr. K. T. Kuo at pathologykimo@gmail.com