The Proportion of Signet Ring Cell Component in Patients with Localized Gastric Adenocarcinoma Correlates with the Degree of Response to Pre-Operative Chemoradiation

BACKGROUND: Patients with localized gastric adenocarcinoma (LGAC), who get pre-operative therapy, have heterogeneous/unpredictable outcomes. Predictive clinical variables/biomarkers are not established. METHODS: We analyzed 107 LGAC patients who had chemoradiation and surgery. LGACs were grouped for (1) presence/absence of signet ring cell histology (SRC) and (2) histologic grade: G2 or G3. %SRC was assessed (0, 1-10, 11-49, and 50-100%) and correlated with pathologic complete response (pathCR) or <pathCR in the resected specimens. RESULTS: Most patients were men (60%), had stage cIII LGAC (50%), and received chemotherapy before chemoradiation (93%). Most had G3 tumors (78%) and SRC (58%). Presence of SRC was associated with a lower rate of pathCR (11 vs. 36%, p = 0.004), and the association remained significant even with a low percentage of SRC (1-10%; p = 0.014). The higher the fraction of SRC, the lower was the probability of pathCR (p = 0.03). G3 and SRC led to a shorter overall survival (OS) (p = 0.046 and p = 0.038, respectively). yp stage independently prognosticated OS and recurrence-free survival (p < 0.001). CONCLUSION: Our novel findings suggest that LGACs with SRC are relatively chemoradiation resistant compared to LGACs without SRC. A higher fraction of SRC is associated with higher resistance. Upon validation/biomarker(s) evaluation, reporting of the fraction of SRC may be warranted.