Abstract
Early papillary gastric adenocarcinoma (EPGA), a well-differentiated gastric adenocarcinoma, is characterized by higher malignancy and worse prognosis compared to other differentiated gastric adenocarcinomas. Therefore, there is a critical need to elucidate its clinicopathological features and mucin expression for accurate diagnosis. The data of 116 cases of EPGA and 116 cases of early well-moderately differentiated tubular gastric adenocarcinoma (ETGA) diagnosed via pathological examination following radical gastrectomy from January 2016 to December 2023 at the Second Hospital of Shandong University were collected. Multivariable logistic regression was used to conduct a comparative analysis of the two groups of variables. The features of histological grading and immunophenotype, particularly mucin expression, were specifically analyzed. The receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic efficacy of potential biomarkers in distinguishing EPGA from ETGA. The features of histological grading and MUC5AC expression in EPGA were specifically analyzed. Additionally, the risk factors of LVI in early gastric cancer (EGC) were assessed. EPGA exhibited significantly larger size (P < 0.001), higher frequencies of elevated appearance (P = 0.001), ulcer formation (P = 0.010) and lymphovascular invasion (LVI, P = 0.050) compared to ETGA. The expression of mismatch repair-deficient (P = 0.005) and MUC5AC (P < 0.001) were significantly elevated in EPGA compared to ETGA. Compared to ETGA, high-grade EPGA exhibited a greater incidence of ulcer formation (P < 0.001), submucosal invasion (P = 0.007), LVI (P = 0.010) and microsatellite instability-high (MSI-H, P < 0.001), whereas low-grade EPGA demonstrated clinicopathological characteristics similar to ETGA. MUC5AC expression was associated with LVI (P = 0.034) and MUC6 (P = 0.017) in EPGA. Moreover, high expression of MUC5AC showed good diagnostic efficiency in distinguishing EPGA (AUC = 0.724, 95% CI = 0.66-0.79). When EGC infiltrated the submucosa (OR = 25.227, 95% CI = 4.017-158.432; P < 0.001) or exhibited MSI-H phenotypes (OR = 10.708, 95% CI = 1.478-77.565; P = 0.019), LVI was more likely to occur. The retrospective study elucidates the clinicopathological features and mucin expression profiles of EPGA. The complex architecture and pronounced nuclear atypia observed in high-grade EPGA are indicative of higher malignancy. Moreover, the high expression of MUC5AC suggests a strong likelihood of EPGA, which may aid in its differentiation. In addition, MSI correlates with the presence of LVI in EGC.