Dr. David Cotter discusses the role of gene expression profiling, including the tests available for diagnosing melanoma and managing patient treatment.
“Gene expression profiling is an exciting new way to interrogate cutaneous problems in our dermatologic patients,” said David Cotter, MD, PhD, who discussed using gene expression profiling (GEP) to individualize care for skin cancer patients at DERM2021.
“Today, with the technology that we have, we can actually look inside of a cell and ask at a very high level with a high level of accuracy, what are the genes actually doing and how does that influence tumor biology?”
According to Dr. Cotter, who is a board-certified dermatologist with a PhD in molecular cell biology and physiology, GEP has a definitive role in the way we manage skin cancer, including pre-biopsy testing and risk prediction of melanoma metastasis, recurrence, and survival.
To Biopsy or Not?
The pre-biopsy test is a tape strip test (DermTech) that can be used to determine whether or not to biopsy a pigmented lesion. It is particularly helpful when ruling out a biopsy on a cosmetically sensitive area such as the breast or nasal tip, said Dr. Cotter.
“…a month ago, a young woman came in with a pigmented lesion on her breast that had enlarged during pregnancy—a very common story. It looked extremely benign. She didn’t want it removed. She didn’t want a scar there… but she was concerned.”
Dr. Cotter used the DermTech test to determine if he needed to biopsy the lesion. The test looks for 2 genes—PRAME and LINC00518— and sometimes a third, called TERT. With a negative predictive value of 99.6%, a negative result is truly negative. In this case, it was negative and the patient was spared both the biopsy and resulting scar.
“We didn’t do the biopsy. And she and I were both very assured with that result.”
The other clinically available GEP tests are indicated post-biopsy and provide additional information for patients diagnosed with melanoma or atypical lesions.
Predicting Risk of Recurrence, Metastasis
“Before gene expression profiling was available, we would follow standard staging that’s been set up by the AJCC [and] the NCCN, and they have pretty strict guidelines to adhere by that are very helpful.”
According to Dr. Cotter, when that was all dermatologists had, it was “good enough.” But with the availability and accuracy of GEP tests, there is now an opportunity to do better.
“The reason why it’s not good enough is because standard staging is going to fail to capture some patients that are going to go on and die from metastatic melanoma.”
As a result, when patients have a positive melanoma diagnosis, Dr. Cotter orders the Decision DX cutaneous melanoma test (Castle Biosciences).
“…it risk-stratifies patients for the risk of metastasis to the node and the risk of recurrence, which are really helpful in terms of managing patients.”
This test, too, is highly accurate, said Dr. Cotter. It has been studied in nearly 6000 patient samples, validated for risk of recurrence, prediction of the likelihood of sentinel lymph node positivity, and melanoma specific survival, and included in 30 peer-reviewed publications.
Addressing Atypical Lesions
For atypical biopsy results, there are additional GEP testing options (myPath Melanoma and DiffDx-Melanoma; Castle Biosciences) to help arrive at a definitive diagnosis.
“Sometimes you’ll biopsy a pigmented lesion, and it comes back atypical, but it’s not a Nevus and it’s not a melanoma.”
Traditionally, the dermatopathologist could perform ancillary testing or send it to a local or national expert for diagnosis.
“[Now] we can actually look inside the cell and ask, what genes are you expressing? And tell me, are those genes associated with melanoma or associated with a benign Nevus?”
Importantly, these tests don’t replace anything a dermatologist is already doing in the diagnostic process, said Dr. Cotter. They provide an opportunity to refine results.
For the Castle test, “It maybe gets someone to a sentinel node procedure that they wouldn’t otherwise have done. Or maybe it deescalates care for a 90-year-old patient with a very, very low risk of having metastatic melanoma who doesn’t need to go to the operating room.”
Both the DermTech and Castle tests are covered by Medicare, said Dr. Cotter.
“I think most patients don’t ever come out more than $50 to $75 per test run… I think if you have a great test, but it costs a million bucks, no one’s ever going to order it, and then no one’s ever going to benefit from that test.”
