Perhaps the most groundbreaking element of the International Melanoma Tissue Bank Consortium (IMTBC), run by AIM of the Melanoma Foundation in Frisco, Texas, is its ability to support prospective research, according to one expert. Rather than waiting for patient results to be known, she said, this capability could allow researchers to update their understanding of dangerous tumors as they evolve.
“This is basically the only prospective study that is planned to see why different melanomas progress differently,” said Maritza Perez, MD, who is not involved in the project. Dermatology Times®. “It’s prospective in that researchers take frozen tumor samples before they know what’s going to happen with the patient.” She is a professor of dermatology at the University of Connecticut School of Medicine in Farmington, Connecticut.
Use of frozen primary tumor specimens will allow preservation of RNA and other proteins typically lost in the formalin-fixed, paraffin-embedded process. Focusing on primary melanomas is essential because these tumors contain the original genetic profile of melanoma. “The metastatic tumor has already induced many more mutations,” Perez said. “You need the original tumor to see the markers that lead to a bad outcome.” For each sample, the tissue bank will also collect complete and de-identified patient information, as well as blood samples and other samples.
In late May, AIM announced the resumption of IMTBC operations after a COVID-related downturn.1 As of March 31, the project had collected a total of 69 samples from 4 initial sites:
- Hillman Cancer Center, University of Pittsburgh Medical Center (Pittsburgh, Pennsylvania)
- Knight Cancer Institute, Oregon Health and Science University (Portland, Oregon)
- California Pacific Medical Center (San Francisco, CA)
- Robert H. Lurie Comprehensive Cancer Center, Northwestern University (Chicago)
Scaling up to an expected initial critical mass of 500 samples will take years, Perez said. “But if you want to do an elegant prospective study, this is the only way to do it.”
Currently, Perez said Dermatology Times®, IMTBC researchers collect data they may not know what to do with at first. But as tumors evolve, she says, perhaps a patient who started with a late TIb melanoma becomes node-positive in 3 years and metastatic in 4. Over time, researchers will try to identify the characteristics or biomarkers that distinguish this tumor from less aggressive ones. .
DecisionDX-Melanoma (Castle Biosciences) extracts DNA from formalin-fixed melanoma samples and determines how much genetic material the sample shares with metastatic breast, lung and other cancers. “It’s a totally different animal,” she said, “but it’s the only tool we have right now to identify potentially very serious melanomas from less serious ones.”
Decoding the human genome was only the first step to understanding the behavior of cancers, including melanoma, Perez added. Without messenger RNA (mRNA) to indicate the functionality of each exon, she says, knowing the structure of the genome is of little clinical use.
The information encoded in mRNA will be crucial for projects like IMTBC, Perez said. If you can decipher the genomic characteristics of malignant melanoma, she explained, you can treat more aggressively from the start. One of his patients, for example, has a nodular melanocytic tumor 3 mm deep, 3 mitoses per cm2 and an ulceration. DecisionDX identified it as stage IIb melanoma. Even if a sentinel lymph node biopsy comes back negative, Perez said, that patient should be eligible for immunotherapy. And identifying specific markers that cause this patient’s tumor to behave aggressively “will be good for the next patient who has the same characteristics and histology in the same tumor type, but smaller.” You can use it as a prognostic tool.
Although physicians’ appreciation of the importance of RNA has increased dramatically over the past 2 decades, collecting RNA poses challenges. “When I do a biopsy for suspected melanoma,” Perez said, “I do a shave biopsy, put it in formalin, and send it to a dermatopathologist. In 24 hours, I have my results.
In contrast, IMTBC requires participating facilities to have a dermatopathologist on site who immediately freezes half of the sample in liquid nitrogen and stores it on site for future use. Outside of research centers like the IMTBC Top 4 sites, Perez said, this approach isn’t practical for the average dermatology practice.
Whether IMTBC will collect enough samples from patients of color is “the $2 million question,” Perez added. Most clinical researchers are keenly aware of the need to include minorities in trials, Perez said, because minorities typically suffer from the same illnesses as white patients and, with melanoma, tend to fare better. badly due to a later diagnosis. However, obtaining an adequate representation of skin color (SOC) can be difficult because melanomas are less common in these patients.
Additionally, patients with SOC are more likely to develop acral lentiginous melanomas, which Perez believes should be among the key criteria signaling a poor melanoma prognosis.2 like deep melanomas, nodular melanomas and a high number of mitoses are generally poor prognoses.
The only reliable way to increase SOC representation in melanoma banks, Perez said, is to have a physician in each location who specializes in SOC and therefore can recruit patients of color. “It has been shown that patients tend to be attracted to physicians who are like and understand them.3.4
Perez reports no relevant financial interests.
1. AIM at the Melanoma Foundation. FAQ and Update on AIM at Melanoma’s International Melanoma Tissue Bank Consortium. https://www.aimatmelanoma.org/faq-and-update-on-aim-at-melanomas-international-melanoma-tissue-bank-consortium/. May 25, 2022. Accessed June 1, 2022.
2. DiCarlo V, Stiller CA, Eisemann N, et al. Does the morphology of cutaneous melanoma explain international differences in survival? Results of 1,578,482 adults diagnosed between 2000 and 2014 in 59 countries (CONCORD-3) [published online ahead of print, 2022 Mar 29]. Br J Dermatol. 2022;10.1111/bjd.21274.
3. Laveist TA, Nuru-Jeter A. Is doctor-patient racial match associated with greater satisfaction with care? J Health Soc Behavior. 2002;43(3):296-306.
4. Hooper J, Shao K, Feng H. Racial/ethnic health disparities in dermatology in the United States Part 1: overview of contributing factors and management strategies [published online ahead of print, 2022 Feb 7]. J Am Acad Dermatol. 2022;S0190-9622(22)00194-3. doi:10.1016/j.jaad.2021.12.061