A biomarker associated with basal cell carcinoma around the eye may help signal which tumors are likely to be aggressive, report researchers from University of Michigan (U-M) at Ann Arbor.

The findings, which appear in JAMA Oncology, may help eliminate some trial and error in matching the right treatments to the right tumor.

Recent research showed that the hedgehog signaling pathway, which is essential for tissue development and growth, is critical in all forms of basal cell carcinoma. A clinical trial at U-M is looking at whether one of two drugs intended to block hedgehog signaling can be an effective way of preserving eyesight in cases of advanced basal cell cancer near the eye. Trials of these drugs in basal cells not limited to the eye found that up to a third of patients had serious side effects.

High Levels of EZH2 and Ki67 Present in Aggressive BCC

With strong early results from that study, the researchers wanted to find a molecular marker to identify basal cell tumors that are more likely to be aggressive, in the eye or elsewhere. They also wanted to identify markers of tumors that might be more likely to benefit from chemotherapy with hedgehog inhibitors. They started with the protein EZH2, which is known to play a key role in several aggressive cancers.

The team analyzed tissue samples from 60 patients with basal cell carcinoma — 30 with a less histologically aggressive type and 30 with an aggressive type of the disease. Using molecular techniques, they tested for expression of EZH2 as well as Ki67, a marker of cell division.

“We found higher levels of both EZH2 and Ki67 in more aggressive tumors. This is the first fundamental step to show that EZH2 is abundant in histologically aggressive forms of these cancers,” says Rajesh Rao, M.D., assistant professor of ophthalmology and visual sciences and of pathology, in a news release.

Several drugs targeting EZH2 in other types of cancer are in the pipeline. The researchers will now look at whether these drugs could expand to basal cell cancers, alone or in combination with hedgehog inhibitors, to improve outcomes. They will also look at whether EZH2 or Ki67 can serve as a marker to help identify patients with an increased risk of cancer recurrence or tumors that are more likely to respond to chemotherapy.