Clinicopathological, immunohistochemical, and overall-survival associations of poorly cohesive gastric carcinoma stratified by signet ring cell percentage

BACKGROUND Poorly cohesive carcinoma (PCC) is a major histological type of gastric cancer characterized by decreased intercellular adhesion and manifests as isolated tumor cells or small, scattered clusters. PCC is morphologically heterogeneous and comprises two pathological components: Signet ring cell carcinoma (SRC) and PCC-not otherwise specified (PCC-NOS). According to the European Consensus, PCC is further classified into three subtypes based on the SRC proportion: SRC (≥ 90%), SRC/PCC-NOS (10% < SRC < 90%), and PCC-NOS (≤ 10%). AIM To comprehensively evaluate the clinicopathological, immunohistochemical, and prognostic profiles of PCC and its subtypes stratified by SRC proportion. METHODS This single-center retrospective cohort study included 1592 patients who underwent gastrectomy for gastric cancer between September 2016 and December 2018, with a loss-to-follow-up rate of 23.6%. Among them, 374 patients were diagnosed with PCC (70 SRC, 171 SRC/ PCC-NOS, and 133 PCC-NOS) and 1218 had non-PCC carcinoma. Propensity score matching (PSM) was performed to minimize selection bias between the PCC and non-PCC groups and among the PCC subtypes. Survival outcomes, clinicopathological features, and immunohistochemical markers were analyzed. RESULTS Five-year overall survival (OS) did not differ significantly between the non-PCC and PCC groups (68.87% vs 69.11%, P = 0.4425), and this finding remained consistent after PSM (P = 0.9189). Among the PCC subtypes, the SRC group presented at an earlier tumor stage. Unadjusted 5-year OS was highest in the SRC group (80.77%), followed by the PCC-NOS (67.80%) and SRC/PCC-NOS (65.03%) groups (P = 0.0460). However, this survival advantage was no longer significant after PSM (P = 0.5820). Immunohistochemical analysis revealed inter-subtype heterogeneity in the expression of Ki67, mismatch repair (MMR) proteins, and programmed death protein ligand 1 (PD-L1). PD-L1 expression tended to be lower in the SRC group, whereas all cases with MMR protein loss were PCC-NOS, while the result remains exploratory and descriptive with the limitation of sample size. CONCLUSION This study demonstrated that PCC as a whole had a prognosis comparable to that of other gastric cancers. However, PCC subtypes exhibited distinct clinicopathological and immunohistochemical profiles, with SRC associated with an earlier stage and a better OS. These findings support the clinical relevance of PCC subclassification and warrant further validation in larger cohorts.