Signet ring gastric and esophageal adenocarcinomas: characteristics and prognostic implications

Controversy exists as to the relevance of the signet ring carcinoma (SRC) histological subtype of esophagogastric adenocarcinoma to long-term prognosis, with some studies reporting a worsened oncological outcome and others no clinically relevant impact. A retrospective analysis of outcomes of patients who underwent surgery with curative intent in two high-volume centers (2000-2015) was undertaken. Tumors were analyzed according to location (esophageal, junctional or gastric). Propensity score matching (PSM) analysis was used to match patients with signet ring histology to those without (195 SRC vs. 573 non-SRC), based on age, tumor location, use of neoadjuvant and adjuvant chemotherapy and pathological stage. A total of 2,500 patients with esophagogastric adenocarcinomas were treated, of whom 198 (7.9%) had signet ring histology. Signet ring tumors were more likely to have positive lymph nodes at pathological analysis (59% vs. 50%, P = 0.009). The 5-year survival rate for patients with early signet ring tumors (Stage 0/1/IIa) was 65% versus 85% for other early cancers (P < 0.003). Patients with esophageal signet ring tumors had a particularly poor prognosis with 23% 2-year survival and none alive at 5 years. With PSM, overall survival (OS) was significantly poorer in the signet ring group (44.3 +/- 8.6 vs. 59.8 +/- 8.5 months, 5-year OS 41% vs. 50%, P = 0.027). Signet ring cells within esophagogastric adenocarcinoma are associated with a poorer prognosis. Genomic studies to identify the composition of such tumors as well as identify strategies to improve treatment for this subtype are warranted.