As reported in the Journal of Clinical Oncology, Ho et al found that tumor-based enhancer of zeste homolog 2 (EZH2) gene or protein expression was independently predictive of prognosis in localized clear cell renal cell carcinoma. EZH2 is a chromatin remodeler implicated in the pathogenesis of clear cell renal cell carcinoma.
The study evaluated the association of EZH2 gene and protein expression with survival in cohorts from The Cancer Genome Atlas (n = 532), The University of Texas Southwestern Medical Center (n = 122), and the Mayo Clinic (n = 1,338). Analyses were adjusted for the prognostic stage, size, grade, and necrosis (SSIGN) score.
In an analysis adjusted for age and SSIGN score, an increased risk of overall mortality was associated with EZH2 high vs low expression (mRNA > 5.36 vs ≤ 5.36 expectation-maximization normalized counts) in The Cancer Genome Atlas cohort (hazard ratio [HR] = 1.54, P = .028), EZH2 high vs low protein expression (> 8.0% vs ≤ 8.0% EZH2-positive nuclei) in The University of Texas Southwestern Medical Center cohort (HR = 2.16, P = .034), and EZH2 high vs low protein expression (> 8.7% vs ≤ 8.7% EZH2-positive nuclei) in the Mayo Clinic cohort (HR = 1.43, P = .00026).
Analysis of renal cell carcinoma–specific death in the Mayo Clinic cohort showed an increased risk with EZH2 high vs low protein expression (HR = 1.97, P < .001). In this analysis, high vs low protein expression was most highly prognostic among patients with low-risk SSIGN tumors (HR = 6.14, P < .001; HRs = 2.12, P < .001, for intermediate-risk and 1.50, P = .27, for high-risk).
The investigators concluded: “EZH2 expression accurately predicts risk of [renal cell carcinoma] death beyond existing clinicopathologic models, particularly in low- and intermediate-risk SSIGN tumors. Further studies are required to incorporate molecular biomarkers into surveillance guidelines and adjuvant clinical trials.”
The study was supported by the Mayo Clinic Center for Individualized Medicine Clinomics Program, National Cancer Institute, and others.
Thai Huu Ho, MD, PhD, of the Mayo Clinic, Phoenix, is the corresponding author of the Journal of Clinical Oncology article.