EZH2 Protein May be a Prognostic Marker for Localized Clear Cell RCC

Data from three independent cohorts suggest that high EZH2 expression may mean a higher risk of death for patients with clear cell renal cell carcinoma.

The prognostic effect of EZH2 protein expression in renal cell carcinoma (RCC) has been controversial. However, a new study is suggesting an association between increased EZH2 expression and a higher risk of death from RCC in three independent cohorts. In addition, the association appeared to be particularly significant in patients classified as low risk or intermediate risk by tumor stage, size, grade, and necrosis (SSIGN) score.
“Our study showed that higher expression of EZH2 in an RCC tumor is not only able to help predict overall which patients will eventually die, but also it had the ability to do so within the categories of those already determined to be low or moderate risk. This was somewhat surprising because when we get into these subcategories of patients, finding a biomarker that can predict outcome can be more challenging,” said Alexander Parker, PhD, associate director for the Center for Individualized Medicine and professor of epidemiology and urology at the Mayo Clinic in Jacksonville, Florida.
The current investigation found that EZH2 expression appears to accurately predict risk of RCC death beyond existing clinicopathologic models. The authors note that results have been conflicting in preclinical models implicating EZH2 in tumorigenesis. They theorize previous findings have been mixed due to differences in EZH2 antibody epitopes influencing EZH2 detection and quantitation.

In this current study, the researchers included three independent cohorts (1,992 tumors). They performed Cox regression to evaluate the association of tumor-based EZH2 gene and protein expression with survival in a cohort from The Cancer Genome Atlas (TCGA; n = 532). Two other cohorts included one from University of Texas Southwestern Medical Center (n = 122) and a cohort from Mayo Clinic (n = 1,338).

EZH2 expression was found to be associated with higher risk of poor outcome following surgery, in a univariate setting and after adjusting for clinicopathologic prognostic factors. Patients in TCGA cohort with EZH2-high gene expression were 1.5 times more likely to experience overall death than patients with EZH2-low expression. Patients in the University of Texas Southwestern Medical Center cohort with EZH2-high protein expression were 2 times more likely to experience overall death than patients with EZH2-low expression, according to the report. In the Mayo Clinic cohort, investigators found that patients with EZH2-high protein expression were 1.4 times more likely to experience overall death.

“If standard of care is a CT scan at 1 year after surgery to check for possible recurrence and we find that a particular patient has a tumor with high expression of EZH2, this would suggest that the scan should be done sooner and perhaps with more frequency because this patient is at greater risk than most patients. It is essentially part of the movement away from ‘one size fits all’,” Parker told OncoTherapy Network.