Linde M van Veenendaal1, Eduardo Bertolli2,3, Catharina M Korse4, W Martin C Klop5, Margot E T Tesselaar1, Alexander C J van Akkooi6. 1. Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands. 2. Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands. 3. Skin Cancer Department, AC Camargo Cancer Center, São Paulo, SP, Brazil. 4. Department of Clinical Chemistry, Netherlands Cancer Institute, Amsterdam, The Netherlands. 5. Department of Head and Neck Surgery, Netherlands Cancer Institute, Amsterdam, The Netherlands. 6. Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands. a.v.akkooi@nki.nl.
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.
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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