Aggressive basal cell skin cancers have higher levels of both EZH2 and Ki67, suggesting these proteins have potential to serve as biomarkers for when basal cell carcinoma has become dangerous.1

Typically, basal cell skin cancers are easily removed, such as those on the arm, leg, or back. However, basal cell skin cancer on the eyelid or invading surrounding is no longer straightforward.

“Basal cell carcinoma around the eye is very common. The eyelids seem to be a magnet for basal cell,” said Alon Kahana, MD, PhD, associate professor of ophthalmology and visual sciences at the University of Michigan Kellogg Eye Center in Ann Arbor.

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“When a patient ignores it and doesn’t get it checked out, it can become bigger and invade deeper, making it much more difficult to treat. To do surgery with clear margins you may damage the muscles that control the eye or the bones of the eye socket, or you might even need to remove the eye. It can be really devastating,” he added.

Even when patients get treated promptly, an incompletely excised tumor on the eyelid can return years later in a much more aggressive form. Further, basal cells anywhere in the body can potentially become aggressive and spread throughout the body.

The hedgehog signaling pathway is recently proven critical to all forms of basal cell carcinoma. The researchers investigated EZH2, known to play a key role in several aggressive cancers, for its potential as a biomarker.

Tissue samples from 60 patients with basal cell carcinoma were examined, half of which were a less aggressive type and half a more aggressive type. The tissues were tested for expression of EZH2 and Ki67.

“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,” said Rajesh Rao, MD, assistant professor of ophthalmology and visual sciences and of pathology at the University of Michigan.

The researchers will next investigate whether drugs targeting EZH2 already in the research pipeline could expand to basal cell cancers. In addition, whether EZH2 or Ki67 can serve as a marker to help identify patients with an increased risk of cancer recurrence or tumors more likely to respond to chemotherapy.

“One of our hopes is that this promising new discovery will bring back some attention to this most common of all cancers,” Kahana says. “Every one of us knows someone who has had basal cell. Our country is filled with survivors.”


1. Rao RC, Chan MP, Andrews CA, Kahana A. EZH2, proliferation rate, and aggressive tumor subtypes in cutaneous basal cell carcinoma [published online ahead of print April 7, 2016]. JAMA Oncology. doi:10.1001/jamaoncol.2016.0021.