TLC as shown in Figure 4C, healthy controls vs. ALC as shown in Figure 4D, and healthy controls vs. both typical and atypical lung carcinoids, as shown in Figure 4E. The AUCs are between 0.693 and 0.766, indicating fair accuracy as a diagnostic test. Figure 4 A novel indirect ELISA detects Ma2 autoantibodies in lung carcinoid patients. Discussion We have selleckchem recently profiled primary SI-NETs and liver metastases by using Affymetrix microarrays and identified that paraneoplastic antigen Ma2 is produced by enterochromaffin cells and neuroendocrine tumor cells [13]. Few studies have correlated paraneoplastic syndrome to patients with midgut carcinoids and lung carcinoids as well [15], [25].

Our finding that Ma2 was consistently detected in primary SI-NET specimens and in a variety of metastasis made it interesting to investigate whether antibodies against Ma2 are present in the blood of SI-NET patients. The main purpose of the present study was to assess whether Ma2 autoantibodies can be used as a specific and sensitive blood-based marker for a more accurate diagnosis and progression of SI-NETs. We set up a novel indirect ELISA able to accurately screen the Ma2 autoantibody levels in serum or plasma samples. We confirmed the specificity of serum Ma2 autoantibodies by using western blot and sequential immunoprecipitation analyses. A central aspect of our investigation is that Ma2 autoantibodies discriminate a large portion of SI-NET patients from healthy controls both considering the diverse tumor categories which reflect different stages of disease and as a whole.

The evaluation of the different levels of Ma2 autoantibodies, which were detectable in the diverse categories of patients, is reliable considering the high values of sensitivity, specificity and AUC values from the ROC analyses. The AUC values are convincing to continue to screen more samples as new SI-NET patients are being diagnosed. This would imply that Ma2 autoantibodies are likely produced early in the development of SI-NETs, with maintenance of steady blood levels during tumor progression. One of the most important clinical problems is to detect early disease as well as to detect early recurrence after surgery with a curative intent. Increased CgA levels in blood is the standard biomarker and considered important in indicating tumor recurrence in most radically operated midgut carcinoid tumor patients [12], [26]. We had the possibility to follow 36 patients with primary tumors operated with a curative intent. We found that the median level of CgA is within the reference range, <4 ng/ml in both groups of patients below and above cutoff level for Ma2 autoantibodies i.e. that CgA levels are not Carfilzomib indicative in this group of patients.