P1.111. The Presence of Signet Ring Cells Predicts Aggressive Chemotherapy Resistance in Esophageal Adenocarcinoma

Abstract

Abstract Topic Esophageal Cancer: Molecular Biology/Pathology Background Esophageal adenocarcinoma (EAC) remains a rapidly rising and poorly controlled malignancy worldwide, despite radical surgery and multimodal therapy. Signet ring cells (SRC) are classically known to signal a more aggressive cancer and are associated with poorer oncologic outcomes, compared to non-signet ring cell adenocarcinoma (NSRC). Little is known, however, regarding the course of this disease in the setting of perioperative chemotherapy. We sought to elucidate the effect of SRC in resectable EAC patients receiving perioperative chemotherapy. Methods A single-centre retrospective chart review was performed of all EAC patients treated with neoadjuvant systemic therapy, followed by esophagectomy, from 2012-2023. Patients receiving preoperative radiation and patients with metastatic disease were excluded. Clinical variables, including tumour histology, clinical staging, treatment regimens, tumour regression grade (TRG), recurrence, and survival, were extracted. Group variables were compared by t-test, chi-squared test, or Fisher’s exact test. A multivariate regression model was used to assess the independent effect of signet ring cells on chemoresistance. Survival curves were estimated by the Kaplan-Meier method. Results 450 patients were included in this study, 51 (11%) of whom had a component of SRC identified on histology. Between the SRC and NSRC cohorts, there were no differences in age, comorbidities, clinical stage, and chemotherapy regimens. SRC tumours had poorer differentiation (86% G3 vs. 40%, p<0.01) and exhibited more chemoresistance (57% TRG3 vs. 33%, p<0.01). Subgroup analysis of poorly differentiated (G3) tumours showed congruent chemoresistive effect (62% TRG3 vs. 34%, p=0.02). On multivariate analysis, the presence of SRC remained an independent predictor of chemoresistance (OR 2.36, 95% CI 1.25–4.59, p<0.01). The SRC cohort showed poorer 5-year OS (36% vs. 47%, p<0.01) and 5-year DFS (23% vs. 39%, p<0.01). Conclusion In the setting of perioperative chemotherapy, the presence of SRC is associated with increased chemoresistance on univariate and multivariate analyses, as well as poorer survival. Our findings suggest increased chemoresistance as a causal mechanism of poorer oncologic outcomes in esophageal SRC adenocarcinomas. Future work is required to understand the biology of this disease and identify potential therapeutic targets.