Role of chromogranin A-derived fragments after resection of nonfunctioning pancreatic neuroendocrine tumors.

Purpose: No single reliable biomarker is available for nonfunctioning pancreatic neuroendocrine tumors (NF-PanNETs). Vasostatin-1 (VS-1), the N-terminal fragment of chromogranin A (CgA), seems to be a more accurate biomarker compared to its precursor. Primary aim was to investigate the ability of VS-1, compared to total-CgA, to assess the effectiveness of surgical resection performed for NF-PanNETs. Secondary aim was to evaluate two additional CgA-derived fragments, pancreastatin (PST) and vasostatin-2 (VS-2), as possible biomarkers for NF-PanNETs.

Methods: Consecutive patients who underwent surgery for NF-PanNETs at San Raffaele Scientific Institute were included (n = 35). Plasma levels of CgA and CgA-derived fragments were measured by Enzyme-Linked ImmunoSorbent Assay (ELISA), preoperatively and postoperatively.

Results: Preoperative VS-1 was significantly higher compared to VS-1 measured on postoperative day 5 (POD5) (pre: 0.338 nM versus POD5: 0.147 nM, P < 0.001), whereas total-CgA significantly increased after surgery (pre: 1.123 nM versus POD5: 1.949 nM, P = 0.006). Overall, 24 patients showed ≥ 1 feature of tumor aggressiveness (T3-T4, nodal/distant metastases, Ki67 > 5%, microvascular/perineural invasion, necrosis). The median percentage decrease in VS-1 plasma levels was 63% (IQR 28-88%) among patients with aggressive tumors, compared to 13% (IQR 0-57%) in the remaining population (P = 0.033). No significant differences in terms of PST (P = 0.870) and VS-2 (P = 0.909) were observed between preoperative and postoperative time.

Conclusion: VS-1 provides an early assessment of surgical efficacy in patients who undergo resection for NF-PanNETs, especially in those with aggressive neoplasms. Total-CgA, PST and VS-2 have no clinical utility in this setting.