Background Gastric malignant neuroendocrine neoplasms (NEN) include neuroendocrine carcinoma (NEC) and mixed neuroendocrine & non-neuroendocrin (MiNEN) containing NEC components. The majority of MiNEN is mixed adenoendocrine carcinoma (MANEC). Because of its rarity, there is a lack of systematic research in improving the understanding of its clinicopathological characteristics and prognosis.
Objective To explore the clinicopathological characteristics and the overall survival rate (OS) of gastric malignant NEN taking gastric adenocarcinoma as reference.
Methods A retrospective case control study was performed in the clinical data about non cM1 gastric malignant NEN and gastric adenocarcinoma patients who underwent surgical treatment in the First Medical Center of Chinese PLA General Hospital from January 2008 to December 2018, and their clinicopathological characteristics were analyzed and compared. An 1:3 Tendency score matching (PSM) was used to adjust the confounding factors between gastric malignant NEN and gastric adenocarcinoma cohort. Kaplan-Meier method was used to draw survival curve. Log-rank test was used to analyze the difference of overall survival (OS) rate among groups. Cox regression model was used to analyze the independent risk factors affecting the prognosis of patients.
Results The clinicopathological information of 5 669 patients was included, including 5 443 (96.0%) cases of gastric adenocarcinoma and 226 (4.0%) cases of gastric malignant NEN. Gastric malignant NEN included 148 cases of NEC and 78 cases of MANEC. There were statistically significant differences between gastric malignant NEN patients and gastric adenocarcinoma patients in age, sex, tumor size, tumor location, surgical approach, type of gastrectomy, T stage, N stage and TNM stage (all P<0.05). A total of 2 875 patients with gastric adenocarcinoma and 215 patients with gastric malignant NEN had complete survival information. After PSM, the OS of patients with gastric adenocarcinoma was significantly better than that of patients with gastric malignant NEN (3-year, 5-year OS: 67.3% vs 58.9%, 59.8% vs 48.3%, P=0.002). Subgroup analysis showed that the OS rate of gastric adenocarcinoma patients was significantly better than that of the NEC patients and the MANEC patients (3-year, 5-year OS rate: 67.3% vs 57.5% and 61.1%, 59.8% vs 50.5% and 44.9%, P＜0.05, respectively). There was no significant difference in OS rate between NEC patients and MANEC patients (P=0.993). NEC and MANEC had no significant difference in age, sex, tumor size, tumor location, surgical approach, type of gastrectomy, T stage, N stage, TNM stage and expression of immune markers. Multivariate analysis showed that age (HR=1.945, 95% CI: 1.249-3.030), tumor size (HR=2.199, 95% CI: 1.029-4.701) and TNM stage (Ⅱ stage vs Ⅰ stage HR=1.669, 95% CI: 0.596-4.670, Ⅲ stage vs Ⅰ stage HR=5.710, 95% CI: 2.197-14.837) were independent risk factors for survival of patients with gastric malignant NEN.
Conclusion Gastric malignant NEN and gastric AC have distinctly different clinicopathological features. Gastric malignant NEN shows stronger infiltration ability and higher invasion, and the OS rate of gastric malignant NEN is significantly worse than that of gastric AC, while NEC and MANEC patients have similar clinicopathological features and OS rate. The patients with age ≥ 60 years, tumor ≥ 3 cm and Ⅲ stage have poor prognosis.
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