Prognostic value of signet-ring cell carcinoma proportion in undifferentiated gastric cancer: Implications for endoscopic treatment decisions

BACKGROUND Poorly cohesive gastric carcinomas are classified based on the proportion of signet-ring cell carcinoma (SRCC) components. In surgically resected gastric cancer, SRCC is diagnosed when the signet-ring cell (SRC) component constitutes ≥ 50% of the entire tumor, whereas poorly cohesive carcinoma (PCC) not otherwise specified is diagnosed when the proportion of the SRC component is < 50% of the entire tumor. The SRCC proportion in PCC varies along the spectrum, and its prognostic significance in gastric cancer remains unclear. AIM To investigate how the proportion of SRCC affects tumor pathology, clinical outcomes, and prognosis and treatment decision-making. METHODS This retrospective study included 1066 patients with PCC who underwent gastric cancer surgery at Seoul National University Bundang Hospital from 2016 to 2023. Patients were classified into four groups based on the SRCC proportion: < 10%, ≥ 10% and < 50%, ≥ 50% and < 90%, and ≥ 90%. Clinicopathological and molecular data were compared between the groups. The correlation between SRCC proportion and pathological factors associated with indications for endoscopic resection in patients with early-stage gastric cancer (EGC) was analyzed. RESULTS A higher SRCC proportion was associated with smaller tumor size, lower tumor stage pathological tumor-node-metastasis, and reduced rates of lymphatic, vascular, and neural invasion (P < 0.001). Notably, the ≥ 90% SRCC group exhibited the highest recurrence-free survival (P = 0.0072) and overall survival (P = 0.0002). In EGC, lower SRCC rates were correlated with increased ulceration, larger tumor size, and deeper submucosal invasion (P < 0.001). CONCLUSION Higher SRCC proportions in the PCC correlate with lower tumor aggressiveness and improved prognosis. Its role in EGC should be validated as a factor influencing therapeutic strategies, including endoscopic submucosal dissection.