For over 30 years, cancer researchers have argued about moles.
Specifically, they’ve debated at what point a skin lesion becomes a melanoma, more commonly known as skin cancer. Some claimed that lesions which looked halfway between a benign mole and a melanoma make up a class of their own, while others held that lesions can only be either harmless or cancerous, with no in-between.
Over 70,000 new melanomas will be diagnosed in the United States in 2015, according to the American Cancer Society. Recently, a team of researchers led by Hunter Shain of the University of California-San Francisco announced at the Society for Melanoma Research convention that they have new data that settles the debate—a better way of telling whether a lesion is on track for becoming melanoma.
Intermediate lesions, Shain said, “are very difficult to study simply because they are difficult to identify,” Shain said. Their appearance lies in a gray zone between obviously benign and obviously malignant. When Shain and the team had eight expert dermatologists try to classify them, there was little agreement.
To get around this problem, the team devised a clever solution, using a characteristic of skin cancer to their advantage. Mature melanomas often lie next to skin tissue that represents earlier stages of the lesion. Taking 37 samples of melanomas from patients, the scientists micro-dissected them into their component sections—healthy skin, precursor lesion, possibly intermediate lesion, and mature melanoma.
The researchers sequenced nearly 300 cancer-related genes in each section of the samples to discover which genes changed at which stage of development. They found that intermediate lesions had some harmless mutations but also some genetic changes that could lead to cancerous cell growth. That told them those lesions did not just look in between—their DNA actually made their behavior intermediate between a mole and a melanoma.
Sorting out the genetic gray zone also gave them a clearer view of how a melanoma develops. “In our study, we observe the canonical order of mutations that allow a melanocyte [a skin cancer cell] to overcome these barriers as it progresses to melanoma,” Shain said.
In the 1980s, some researchers described an intermediate lesion as a “dysplastic nevus,” while others argued that the term would lead to confusions in melanoma diagnosis and shouldn’t be used. Shain’s team avoided using the term “dysplastic nevus.”
David Elder of the University of Pennsylvania, who coined the term “dysplastic nevus syndrome” in 1980, attended the team’s presentation in San Francisco. “I think this is an important step forward,” Elder said. “And it does add materially to our understanding of a question that has certainly been hotly debated in our community for many years.”
While the study’s authors didn’t use his terminology, Elder said they are basically describing the same thing. He said that at the presentation, “I asked the question, ‘Were these intermediate lesions dysplastic nevi or were they something else?’ And the response was, ‘Well, yes, they are.’” Elder agreed that using the term could distract from the study’s main message.
Iwei Yeh of UC-San Francisco, a co-author of the study and one of the eight expert dermatologists, said that the new genetic data will allow the next stage of research to narrow the list of suspects for which mutations are most likely to lead to melanoma. Researchers could observe people with intermediate lesions and see which ones develop cancer. Then, they could use those genes as diagnostic signals for a mole on track to become malignant.
“I think that kind of ties into this whole idea of personalized medicine,” Yeh said. “What are the individual alterations that are really contributing to the person’s cancer, and what does that mean for them in terms of their outcome?”
Elder said this kind of study could reduce unnecessary procedures to remove harmless moles, saving time for both doctors and patients.
“More precise diagnosis could be very valuable in more appropriate precision treatment of these lesions,” he said. “If you don’t need to do [a procedure], you don’t want to do it.”
Photo credit: NIH