Objective  To analyze the clinicopathological features and prognostic factors of high-grade G3 gastroenteropancreatic neuroendocrine tumors (GEP NETs).

  Methods  A retrospective analysis was conducted on 86 patients diagnosed with G3 GEP NET and treated at our hospital from September 2012 to July 2019. All clinical and pathological data were summarized. The univariate log-rank test and multivariate Cox regression model were used to analyze the prognostic factors.

  Results  Among the 86 patients with G3 GEP NET, the primary tumor sites were the pancreas, the gastrointestinal tract, and unidentified in 40, 37, and 9 patients, respectively. Microscopically, the tumors were well-differentiated and showed an organoid or a nest-like growth pattern, with focal pseudo-adenoid, fine cord, or ribbon-like structures. Immunohistochemical analysis showed that the Ki67 index ranged from 21% to 60%, with a median value of 30%. The positive expression rate of SSTR2 was 83.9% (26/31), and no microsatellite instability or abnormal expression of p53 was found in the detected cases (0/24 and 0/11, respectively). Follow-up was attended by 76 patients, of whom 27 (35.5%) died during the period. The median survival time was 48.6 months (95% confidence intervalCI:26.6-70.6 months). Univariate analysis showed that radical resection and distant metastasis could significantly influence the overall survival (P < 0.05), but there were no significant differences in age, sex, primary site, serum NSE (neuron specific enolase, NSE) level or Ki67 index (P>0.05). Multivariate analysis showed that distant metastasis at diagnosis was an independent risk factor for the patients' overall survival (P=0.01, hazards ratio=7.33, 95% CI:1.56-34.10).

  Conclusion  The diagnosis of G3 GEP NET depends on histopathological morphology and immunohistochemistry. Distant metastasis is a major clinical feature and prognostic factor.