Prognostic and therapeutic impact of the chromosome 20q13.2 ZNF217 locus amplification in ovarian clear cell carcinoma

BACKGROUND: The goal of this study was to examine the clinical significance of ZNF217 amplification and assess whether ZNF217 could be a potential therapeutic target in ovarian clear cell carcinoma (OCCC). METHODS: ZNF217 expression and amplification in OCCC was assessed by immunohistochemistry, fluorescence in situ hybridization, and clinical data collected via a retrospective chart review. ZNF217 gene knockdown using silencing RNA (siRNA) was used to assess ZNF217 functions in OCCC cell lines. RESULTS: Gene amplification was identified in 12 of 60 (20.0%) OCCCs. ZNF217 copy number correlated significantly with ZNF217 protein expression (r = 0.341; P<.01). ZNF217 amplification correlated significantly with shorter progression-free (P =.0042) and overall (P =.0199) survival. There were nonsignificant trends between high ZNF217 protein expression and poor progression-free (P =.2594) and overall (P =.2199) survival. Multivariate analysis revealed ZNF217 gene amplification to be an independent prognostic factor for progression-free and overall survival after standard platinum agent-based chemotherapy (P =.0339 and P =.031, respectively). Profound growth inhibition and apoptosis were observed in ZNF217 siRNA-treated cancer cells with gene amplification compared with cancer cells with ZNF217 moderate expression without ZNF217 gene amplification or with low ZNF217 expression. CONCLUSION: These findings indicate that ZNF217 overexpression is critical to growth and survival of OCCCs with ZNF217 gene amplification. Furthermore, they suggest that ZNF217 siRNA-induced phenotypes depend on amplification status of OCCCs. Therefore, ZNF217-targeted therapy may benefit OCCC patients with ZNF217 amplification.