At this year’s congress of the European Academy of Dermatology and Venereology (EADV), an innovative research paper was presented that used a promising methodology of tumor-specific profiling to detect antibodies specifically present in stage I and II melanocytic tumors.
In the study by a research team led by Dr. Cristina Vico-Alonso, Victorian Melanoma Service, Melbourne (Australia), an array-based method was used to analyze blood samples from 199 patients with stage I and II melanoma and compare them with blood samples from 38 healthy individuals [1,2]. The blood samples were taken at initial diagnosis and within 30 days of a surgical procedure with curative intent.
Multi-parameter signature increases diagnostic value
Melanoma is a type of skin cancer with a high mutation rate that produces immunogenic markers that trigger an immune response, resulting in the development of antibodies against so-called cancer/testis antigens (CTAg) [3,4]. These CTAg lead to the production of specific antibodies that act as early diagnostic and prognostic markers for melanoma. In the study by Dr. Vico-Alonso and colleagues, specific IgG antibodies against three tumor antigens were identified as promising diagnostic biomarkers for early-stage melanoma. The AUC (area under the curve) valuesranged from 0.857-0.981 in the cohort of the exploratory part of the study (“discovery” cohort) and from 0.824-0.985 in the internal validation cohort [1]. Of the three markers identified, one showed an AUC value of 0.9805 in the discovery cohort** with 98% sensitivity and 76% specificity, and 0.9846 in the validation cohort with 99% sensitivity and 82% specificity. “These results indicate that 99% of melanoma patients in the validation cohort were positive for these markers, while 82% of healthy individuals were correctly identified as negative using the recommended threshold,” explained Dr. Vico-Alonso [2]. “While 18% of healthy individuals were incorrectly identified as positive for this marker, combining it with the other two markers into a multiparameter signature improved diagnostic accuracy,” she said [2]. Based on the validation data, only 1% of melanoma patients would have a negative test for this top marker, suggesting that a negative result is highly likely to rule out the presence of melanoma.
** The discovery cohort is used to detect promising biomarkers, while the internal validation cohort is used to confirm that these biomarkers are reliable and valid in another group of participants.
| Conclusion Early detection of melanoma remains a dermato-oncologic challenge, but these research findings raise hopes for more effective, non-invasive diagnostic tools. Reliable, early detection allows for earlier surgical and other therapeutic interventions, resulting in fewer patients with advanced disease and improved outcomes [5]. “These methods of early detection can be integrated into current routine melanoma screening to provide additional information, especially in unclear cases, and potentially avoid unnecessary procedures,” says Dr. Vico-Alonso [2]. |
Can results be replicated in real-world cohorts?
“It is important to note that this cohort included healthy individuals with no previous or current cancer and that individuals at high risk of developing melanoma were excluded,” explained Dr. Vico-Alonso, adding: “Further research in a real-world cohort is needed to determine whether these findings hold true even when confounding factors, such as comorbidities, are taken into account” [2]. Data from a second, external validation cohort may lead to further insights. “A significant advantage of this array-based method is its tumor type-agnostic nature,” Dr. Vico-Alonso added. “CTAg are expressed in many solid tumors, which opens up a broad field of application far beyond melanoma for the diagnostic signature identified here. Whereby the specific related antigen combination is specific for melanoma. We are currently using the array-based method to identify candidates for a diagnostic “pan-cancer” test, initially focusing on melanomas, as well as lung, colon and pancreatic carcinomas,” the expert revealed [2]. “In previous research, we have identified an antigen signature that is specific for advanced-stage melanomas associated with more aggressive disease or metastasis. Recently, we have also discovered another distinct antigen signature that can differentiate between stage III melanoma patients with vs. without recurrence,” said Dr. Vico-Alonso [2].
Congress: EADV Annual Meeting
Literature:
- Vico-Alonso C, et al: Early detection of melanomas using circulating tumor-specific antibodies. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024.
- “Tumor-specific antibodies able to detect melanoma in its earliest stages, new study shows”, EADV Annual Meeting, Amsterdam, 26.09.2024.
- Heistein JB, Acharya U, Mukkamalla SKR: Malignant melanoma. In StatPearls. Treasure Island, FL: StatPearls Publishing. 2024, Retrieved from www.ncbi.nlm.nih.gov/books/NBK470409.
- Õunap K, et al: Antibody response against cancer-testis antigens MAGEA4 and MAGEA10 in patients with melanoma. Oncology Letters 2018, 16(1): 211-218. https://doi.org/10.3892/ol.2018.8684.
- Davis LE, Shalin SC, Tackett AJ: Current state of melanoma diagnosis and treatment. Cancer biology & therapy 2019; 20(11): 1366-1379.
InFo ONKOLOGIE & HÄMATOLOGIE 2024; 12(6): 32 (published on 11.12.24, ahead of print)
DERMATOLOGIE PRAXIS 2024; 34(6): 39
