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Higher EZH2 and Ki67 Expression May Be Associated With Aggressive Basal Cell Carcinoma

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Key Points

  • Higher EZH2 expression was associated with more-aggressive basal cell carcinoma.
  • EZH2 may constitute a target in basal cell carcinoma and other cancers.

In a study reported in a research letter in JAMA Oncology, Rao et al found that high expression of EZH2 and Ki67 was associated with more-aggressive basal cell carcinoma.EZH2 is a histone methyltransferase of the polycomb repressive complex 2. EZH2 overexpression or gain of function mutations has been found in medulloblastoma—which, like basal cell carcinoma, is associated with the hedgehog signaling pathway—and in a number of other aggressive solid tumors.

EZH2 Expression

In the study, Ki67 proliferation index and EZH2 H score (0–2) were assessed in 30 histologically aggressive and 30 less-aggressive basal cell carcinoma samples. Mean Ki67 proliferation index was 35.7% in aggressive tumors vs 23.3% in less-aggressive tumors (P < .001). Mean EZH2 H score was 1.27 vs 0.77 (P < .001). Ki67 positivity and EZH2 H score were positively correlated among all tumors, more-aggressive tumors (r = 0.53, P = .003), and less-aggressive tumors (r = 0.59, P < .001).

The investigators concluded: “Our data reveal that EZH2 expression correlates with the proliferation marker Ki67 and with aggressive basal cell carcinoma subtypes…. Future studies are needed to determine whether EZH2 and/or Ki67 expression in basal cell carcinoma may enable risk stratification of response to surgical and anti–hedgehog-based therapies, whether hedgehog and EZH2 pathways represent separate or interdependent targetable pathways in basal cell carcinoma, and whether combining anti-hedgehog and anti-EZH2 drugs would have therapeutic advantage for aggressive basal cell carcinoma.”

They noted that early-phase trials investigating EZH2 as a biomarker or assessing the effects of EZH2 inhibition are under way in medulloblastoma, lymphomas, and other solid tumors.

The study was supported in part by the National Institutes of Health and Genentech, Inc.

Alon Kahana, MD, PhD, of the Comprehensive Cancer Center, University of Michigan, Ann Arbor, is the corresponding author of the JAMA Oncology research letter.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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