The Clinical Utility of Neuron-Specific Enolase (NSE) Serum Levels as a Biomarker for Merkel Cell Carcinoma (MCC)

Abstract

Background

No adequate biomarker for Merkel cell carcinoma (MCC) has been identified. Serum neuron-specific enolase (NSE) has been tested and is commonly used as a biomarker for several other small cell malignancies. However, the role of NSE in MCC is still unclear. The purpose of this study was to investigate the role of NSE as a biomarker in MCC.

Methods

A prospective cohort of MCC patients was analyzed using Kaplan–Meier curves with log-rank test, ROC curves, Cox regression, and mixed models. A separate evaluation was performed for patients treated with immunotherapy.

Results

Eighty-four patients were included [47 males, median age 71 years, stages I & II, III, and IV MCC in respectively 39 (46%), 42 (50%), and 4 (3%) patients at time of diagnosis] with 565 NSE samples (median 15; interquartile range 12.6–22 ng/ml). Baseline NSE had no association with prognosis. NSE correlated with extent of disease (P = 0.01) and increased with 15 ng/ml per class (no tumor load, localized MCC, regional or distant metastases, respectively). NSE was able to detect progression (AUC 0.89). A NSE of 18.2 ng/ml was considered the most optimal level for clinical use (sensitivity 91%, specificity 78%, PPV 48%, NPV 98%). During immunotherapy (N = 23; 248 NSE values), all complete responders (N = 10) had a normalized NSE (< 18.2 ng/ml), all partial responders (N = 5) had a decreasing NSE. In nonresponders (N = 8), all NSE levels remained elevated.

Conclusions

NSE could be a valuable biomarker in MCC. NSE correlates with extent of disease; it is able to rule out progression and distinguishes responders from nonresponders during immunotherapy.

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Correspondence to Alexander C. J. van Akkooi MD, PhD.

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Alexander van Akkooi: Advisory board/Consultancy: Amgen, Bristol-Myers, Novartis, MSD-Merck, Merck-Pfizer, 4SC: all paid to institute, not related to submitted work. Research grant: Amgen, Bristol-Myers Squibb, Novartis: all paid to institute, not related to submitted work. All other authors have declared no conflicts of interest related to our study.

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van Veenendaal, L.M., Bertolli, E., Korse, C.M. et al. The Clinical Utility of Neuron-Specific Enolase (NSE) Serum Levels as a Biomarker for Merkel Cell Carcinoma (MCC). Ann Surg Oncol (2020). https://doi.org/10.1245/s10434-020-08656-7

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