The prognostic value of neuroendocrine differentiation in patients with undifferentiated-type gastric adenocarcinoma.

Abstract

20 Background: Neuroendocrine carcinoma (NEC) of the stomach is defined as carcinoma having prominent (>70%) neuroendocrine differentiation (NED), and is well known to be highly malignant tumor with extremely poor overall survival time. However the biological meaning of less NED in gastric adenocarcinoma is still unclear. The aim of this study is to identify the prevalence of NED in undifferentiated type gastric adenocarcinoma (UDGA) and to clarify the prognostic value of NED. Methods: A total of 112 patients with advanced UDGA who underwent curative resection at Shizuoka Cancer Center between January 2004 and December 2006 were included. We performed immunohistochemical analysis for neuroendocrine markers, and classified patients into four groups according to the result of the immunohistochemical study as follows: NEC group (n=6), NED > 70%; MANEC (mixed adenoneuroendocrine carcinoma ) group (n=0), 30-70%; NED+ group (n=46), 1-30%; NED- group (n=60), NED < 1%. In the present study, clinicopathological features were compared between the NED+ and NED- groups and independent prognostic factors were identified. Results: The patients in the NED+ group were significantly younger (61y) than the NED- group (63y, p=0.035). There were no differences in sex, tumor depth, lymph node metastasis, macroscopic type, tumor size, and histological type between the two groups. The five-year survival rates of the NED+ and the NED- groups were 75.7% and 56.5%, respectively. Overall survival was significantly better in the NED+ group than in the NED- group (p=0.030). Cox-proportional hazard model revealed that tumor invasion deeper than T3 (HR, 2.387; 95% CI, 1.114-5.114; p=0.025), lymph node involvement (HR, 3.000; 95% CI, 1.346-9.685; p=0.007) and presence of NED (HR, 0.478; 95% CI, 0.236-0.969; p=0.041) were selected as independent prognostic factors. Conclusions: The frequency of NED in UDGA was 41.1%. The long-term outcome in the NED+ group was better than that in the NED- group. Therefore, UDGA with NED might be clinicopathologically different from the NEC of the stomach and further large scale study should be warranted to determine the biological behavior and to estimate the proper treatment strategy.