ObjectiveTo analyze the predictive value of P504S for pathological upgrading of gastric low-grade intraepithelial neoplasia (LGIN) after endoscopic submucosal dissection (ESD). MethodsData of 117 patients (119 lesions) who underwent ESD for LGIN at Huadong Hospital from January 2015 to March 2019 were analyzed retrospectively. Biopsy and ESD specimens were collected. According to pathology, specimens were divided into the LGIN group (postoperative pathology of non-upgrade) and the upgrade group (postoperative pathology of upgrade). The positive rates of P504S were compared between biopsy and postoperative specimens of the LGIN group, and between biopsy and postoperative specimens of the upgrade group. The consistency of the expression of P504S was examined between the biopsy specimens and the postoperative specimens in the LGIN group and the upgrade group. Receiver operator characteristic (ROC) curve of the prediction of pathological upgrading was drawn by the results of P504S in biopsy, and the cutoff value of immunohistochemical staining score was calculated. ResultsThe positive rate of P504S in the biopsy specimens of the LGIN group (46.8%, 36/77) was lower than that in the biopsy specimens of the upgrade group (73.2%, 30/41) with significant difference (P=0.006). The positive rate of P504S in the postoperative specimens of the LGIN group (51.9%, 40/77) was lower than that in the postoperative specimens of the upgrade group (82.9%, 34/41) with significant difference (P=0.001). In the LGIN group, the positive rate of P504S in biopsy specimens (46.8%, 36/77) was lower than that in postoperative specimens (51.9%, 40/77) without significant difference (P=0.289). The expression of P504S was consistent between biopsy specimens and postoperative specimens with good consistency(K=0.793, P＜0.001). In the upgrade group, the positive rate of P504S in biopsy specimens (73.2%, 30/41) was lower than that in the postoperative specimens (82.9%, 34/41) without significant difference (P=0.219). The expression of P504S was consistent between biopsy and postoperative specimens, and the consistency was general (K=0.579, P＜0.001). ROC curve was drawn for the prediction of pathological upgrading by the results of P504S in biopsy, and the cutoff value of immunohistochemical staining score was 100. The sensitivity and specificity of pathological upgrading for positive result were 0.659 and 0.740, respectively. ConclusionP504S staining of the postoperative specimens facilitates identification of the degree of gastric mucosal neoplasia. When the cutoff value of staining score is 100, the staining of P504S in biopsy tissue plays a role in predicting the pathological upgrading.