Abstract
Simple SummaryImmunotherapy and targeted therapy are widely accepted for stage III and IV melanoma patients. Clinical investigation of adjuvant therapy in stage II melanoma has already started. Therefore, methods for relapse prediction in lower stage melanoma patients apart from sentinel node biopsies are much needed to guide (neo)adjuvant therapies. Gene scores such as the “DecisionDx-Melanoma” and the “MelaGenix” score can help assist therapy decisions. However, a seven-marker immunohistochemical signature could add valuable feasibility to the biomarker toolbox.Background: We aim to validate a seven-marker immunohistochemical signature, consisting of Bax, Bcl-X, PTEN, COX-2, (loss of) ß-Catenin, (loss of) MTAP and (presence of) CD20, in an independent patient cohort and test clinical feasibility. Methods: We performed staining of the mentioned antibodies in tissue of 88 primary melanomas and calculated a risk score for each patient. Data were correlated with clinical parameters and outcome (recurrence-free, distant metastasis-free and melanoma-specific survival). Results: The seven-marker signature was able to identify high-risk patients within stages IB-III melanoma patients that have a significantly higher risk of disease recurrence, metastasis, and death. In particular, the high sensitivity of relapse prediction (>94%) in sentinel negative patients (stages IB–IIC) was striking (negative predictive value of 100% for melanoma-specific survival and distant metastasis-free survival, and 97.5% for relapse-free survival). For stage III patients (positive nodal status), the negative predictive value was 100% with the seven-marker signature. Conclusions: The seven-marker signature can help to further select high-risk patients in stages IIB-C but also in earlier stages IB–IIA and be a useful tool for therapy decisions in the adjuvant and future neo-adjuvant settings. Stage III patients with measurable lymph node disease classified as high-risk with the seven-marker signature are potential candidates for neoadjuvant immunotherapy.
Highlights
The incidence of cutaneous melanoma is rising worldwide [1]
Of patients with positive nodal status (n = 19), almost four times more melanomas were classified as high-risk
Our results show that risk assessment with the seven-marker signature could be expanded to patients with negative nodal status, including stage IB–IIC patients
Summary
The incidence of cutaneous melanoma is rising worldwide [1]. The risk of disease recurrence increases with tumor thickness. For patients with a Breslow thickness of 1 mm (or 0.8 mm and other risk factors such as ulceration, increased mitotic rate or younger age) a sentinel node biopsy for risk stratification and decision of adjuvant therapy should be performed [2,3]. Results: The seven-marker signature was able to identify high-risk patients within stages IB-III melanoma patients that have a significantly higher risk of disease recurrence, metastasis, and death. Conclusions: The seven-marker signature can help to further select high-risk patients in stages IIB-C and in earlier stages IB–IIA and be a useful tool for therapy decisions in the adjuvant and future neo-adjuvant settings. Stage III patients with measurable lymph node disease classified as high-risk with the seven-marker signature are potential candidates for neoadjuvant immunotherapy
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