Abstract

Background and Objective: BLyS (B-Lymphocyte stimulator) is over-expressed in several tumoral settings, with direct or indirect effects on neoplastic proliferation and possibly representing a therapeutic target. In this study, we explored the role of BLyS in a large population of patients with neuroendocrine tumors (NETs).

Methods: The study analyzed the stored sera of 124 consecutive unselected patients with NETs: 36 lung carcinoids (24 typical, 12 atypical), 47 gastroenteric tract and 41 pancreatic (30 non-functioning and 11 functioning: 9 insulinomas, 2 glucagonomas). In 23 cases, BLyS was repeatedly assessed during the follow-up and the disease was monitored (progression, stabilization or remission) according to the RECIST criteria. Patients were compared to 92 age and sex-matched blood donors (BDs). Serum levels of BLyS and Chromogranin A (CgA) were analyzed by ELISA.

Results: NET patients showed significantly higher BLyS levels than BDs (1274±809 pg/ml vs. 587±173 pg/ml; p<0.0001). BLyS correlated weakly with CgA (r=0.19 and p=0.035) but did not correlate with Ki67, grading, metastasis, histological type and site. In patients with sustained remission after surgery, BLyS and CgA both showed a gradual reduction over time. Patients with progressing disease showed higher BLyS levels compared to stable patients (1524±694 pg/ml vs. 1168± 373 pg/ml; p= 0.033). BLyS serum levels remained stable in remission and therapy-controlled patients, while increased in the follow-up of progressing cases.

Conclusion: Higher BLyS levels identify patients with a more severe disease, characterized by progression despite treatments, possibly representing a factor implicated in the proliferation of the neoplastic cells or in sustaining the neoplastic environment.

Keywords: B-Lymphocyte stimulator, neuroendocrine tumors, prognosis, insulinoma, somatostatin, chromogranin A.

Graphical Abstract