New Way Forward for the Diagnosis and Management of Gastroenteropancreatic Neuroendocrine Tumors with an LC-MS/MS Panel of Indole Biomarkers

Diagnosis and surveillance of gastroenteropancreatic neuroendocrine tumors (GEP-NETs)2 involve a repertoire of several different biochemical tests with some differences in utility according to classifications and guidelines from the North American Neuroendocrine Tumor Society (1) and the European Neuroendocrine Tumor Society (2). Measured biomarkers include plasma chromogranin A, urinary or plasma 5-hydroxyindole acetic acid, platelet or whole blood serotonin, serum neuron-specific enolase, and, depending on presentation, a variety of peptides such as gastrin, vasoactive intestinal peptide, and several pancreatic-specific peptides (3). Measured alone for screening, these biomarkers have limited clinical sensitivity, but when positive they can be further useful for patient management, including therapeutic monitoring. Some of the more commonly measured biomarkers, such as chromogranin A, suffer from poor clinical specificity or may be rendered pointless to measure by medications (e.g., proton pump inhibitors) or associated clinical conditions (e.g., renal failure). At the routine laboratory level, maintaining multiplicities of tests for such relatively rare tumors can be cost-prohibitive. Thus, measurements available for clinicians to make the diagnosis or monitor patients can be limited. To address the above issues, van Faassen and colleagues present in this issue of Clinical Chemistry a novel LC-MS/MS method for the measurement of four indole biomarkers in platelet-rich plasma (4). The method is made possible by a derivatization step utilizing propionic anhydride. The question is why use derivatization when one of the advantages of liquid over gas chromatographic front ends in mass spectrometry is to escape such extra steps. First, however, …