Stage-Stratified Prognosis of Signet Ring Cell Histology in Patients Undergoing Curative Resection for Gastric Adenocarcinoma

The prognosis of signet ring cell (SRC) gastric adenocarcinoma is regarded as poor, although studies addressing outcomes in relation to non-SRC tumors are conflicting. Our objective was to compare the survival of SRC tumors with stage-matched intestinal-type tumors in a cohort of Western patients. Review of a prospectively maintained database identified 569 patients undergoing curative resection (R0) from 1990 to 2009. Patients were divided into three histologic groups on the basis of the Lauren classification: SRC (n = 210), intestinal well- or moderately differentiated (WMD, n = 242) disease, and intestinal poorly differentiated (PD, n = 117) disease. Patient demographics, clinicopathologic features, and postoperative outcomes were determined. Stage-stratified disease-specific mortality was calculated and multivariate analysis performed. When compared with WMD and PD tumors, SRC tumors were associated with younger age (63 years SRC vs. 71 years WMD and 72 years PD, p < 0.0001) and with female sex (58 % SRC vs. 40 % WMD and 40 % PD, p = 0.0003). Median follow-up was 115 months. Patients with stage Ia SRC lesions had a better 5-year disease-specific mortality compared with stage-matched intestinal-type tumors (0 % SRC vs. 8 % WMD and 24 % PD, p = 0.001). In contrast, SRC patients with stage III disease fared significantly worse (78 % SRC vs. 54 % WMD and 72 % PD, p = 0.001). On multivariate analysis, the risk of death from gastric cancer comparing all three groups was lowest for SRC in stage I and highest for SRC in stage III disease (stage III hazard ratio: SRC 1 vs. 0.47 WMD and 0.85 PD). When compared with intestinal-type tumors, SRC tumors at early stages are not necessarily associated with poor outcomes.