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Article

Identifying High-Risk Tumors within AJCC Stage IB–III Melanomas Using a Seven-Marker Immunohistochemical Signature

Department of Dermatology, Allergology and Venereology, University Medical Center, 04103 Leipzig, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally.
Academic Editors: Samia Mourah and Barouyr Baroudjian
Cancers 2021, 13(12), 2902; https://doi.org/10.3390/cancers13122902
Received: 19 May 2021 / Revised: 5 June 2021 / Accepted: 7 June 2021 / Published: 10 June 2021
(This article belongs to the Special Issue Targeted Therapies and Immunotherapies in Metastatic Melanoma)
Immunotherapy 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. View Full-Text
Keywords: biomarker; relapse; immunotherapy; targeted therapy; melanoma biomarker; relapse; immunotherapy; targeted therapy; melanoma
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MDPI and ACS Style

Reschke, R.; Gussek, P.; Ziemer, M. Identifying High-Risk Tumors within AJCC Stage IB–III Melanomas Using a Seven-Marker Immunohistochemical Signature. Cancers 2021, 13, 2902. https://doi.org/10.3390/cancers13122902

AMA Style

Reschke R, Gussek P, Ziemer M. Identifying High-Risk Tumors within AJCC Stage IB–III Melanomas Using a Seven-Marker Immunohistochemical Signature. Cancers. 2021; 13(12):2902. https://doi.org/10.3390/cancers13122902

Chicago/Turabian Style

Reschke, Robin; Gussek, Philipp; Ziemer, Mirjana. 2021. "Identifying High-Risk Tumors within AJCC Stage IB–III Melanomas Using a Seven-Marker Immunohistochemical Signature" Cancers 13, no. 12: 2902. https://doi.org/10.3390/cancers13122902

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