Biomarker Increases Understanding of Aggressive Basal Cell Carcinoma

Researchers believe EZH2 could be a potential biomarker for aggressive basal cell carcinoma located on the eyelid or surrounding the eye, a recent article in JAMA Oncology found.

Most basal cell skin cancers can easily be removed when located on a patient’s arm, leg, or back. However, when the cancer is found on the eyelid or begins to invade surrounding tissue, it makes treatment more complicated.

Recent research has found that the hedgehog signaling pathway is critical in all forms of basal cell carcinoma.

Strong data results from these prior studies inspired researchers to find a molecular marker to identify basal cell tumors that are more likely to be aggressive. Additionally, investigators hoped to identify markers of tumors that would more likely benefit from chemotherapy with hedgehog inhibitors.

“Basal cell carcinoma around the eye is very common,” said researcher Alon Kahana, MD, PhD. “The eyelids seem to be a magnet for basal cell. 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.”

Researchers began their study with the EZH2 protein, known to play a key role in several aggressive cancers. Tissue samples from 60 patients with basal cell carcinoma were analyzed, 30 of which had a less histologically aggressive form of the disease and 30 with an aggressive type.

Researchers used molecular techniques to test for expression of EZH2 and Ki67, a marker of cell division.

“We found higher levels of both EZH2 and Ki67 in more aggressive tumors,” said researcher Rajesh Rao, MD. “This is the first fundamental step to show that EZH2 is abundant in histologically aggressive forms of these cancers.”

Currently, there are several EZH2 targeting drugs being developed for other forms of cancer. Researchers will start to examine whether these drugs could expand to basal cell cancers, either alone or in combination with hedgehog inhibitors, to improve patient outcomes.

EZH2 or Ki67 will also be examined to determine if they can serve as a marker for identifying patients with an increased risk of cancer recurrence or tumors that are 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 said. “Every one of us knows someone who has had basal cell. Our country is filled with survivors.”