Abstract

Aim of the study: B-Lymphocyte Stimulator (BLyS), a key regulator of B-cell homeostasis, was recently involved in the regulation of malignant cell survival in both hematological and non-hematological cancers. In this study we analyzed the possible role of BLyS in neuroendocrine tumors (NET). Methods: Sixty-two consecutive unselected patients with a diagnosis of NET were enrolled in the study. According to the clinical course, patients were classified in 3 subgroups: patients with evidence of persistent but stable disease (n = 19), patients in remission (n = 13) and patients with evidence of recurrent disease (progressive patients, n = 30). Patients were compared to 77 sex-matched blood donors (HBDs). BLyS and Chromogranin A (CgA) serum levels were analyzed by ELISA. Results: Overall, NET patients presented more elevated BLyS levels than HBDs (1195± 568 pg/ml vs 666± 240 pg/ml; p < 0.0001) and BLyS levels correlated with tumor differentiation. Patients with stable disease or in remission presented with significant lower BLyS levels than patients with disease progression (906±273 pg/ml versus 1503±637 pg/ml; p < 0.0001). Patients with metastases displayed higher BLyS levels than patients without metastases (1391±724 pg/ml versus 1079±422 pg/ml; p=0.022). Of note, BLyS levels during the follow-up (after 6.6±2.8 months) demonstrated a significant increase in progressive patients (from 1576±927 pg/ml to 2003±1268 pg/ml; p=0.0107), while remained substantially unchanged in stable/remission cases (from 1103±427 pg/ml to 1060±400 pg/ml; p=0.52). In contrast, CgA in the same series showed contradictory change Conclusions: Elevated BLyS levels characterized patients with NET and BLyS appears as a new potential marker in the management of these neoplastic diseases.

Keywords: BLyS/BAFF, neuroendocrine tumors, carcinoids, Chromogranin A, biomarkers, follow-up, metastasis, somatostatin, pathogenesis, prognosis, specificity, sensibility