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.