HER2低表达食管胃结合部腺癌的临床病理特征及预后OA

Objective:Esophagogastric junction adenocarcinoma(EGJA)is a common malignancy of the digestive tract.Due to its unique anatomical location and high tumor heterogeneity,clinical management and prognostic assessment remain challenging.Human epidermal growth factor receptor 2(HER2)is a key therapeutic target in gastric cancer.Current clinical research has largely focused on HER2-positive tumors,while studies on the clinicopathological features and prognosis of HER2-low EGJA remain limited.This study aims to analyze the clinicopathological characteristics,influencing factors,and prognostic features of HER2-low EGJA,providing theoretical and practical guidance for precise pathological diagnosis and individualized targeted therapy. Methods:Clinical data from 738 patients with EGJA treated at Anyang Tumor Hospital between January 2014 and December 2024 were retrospectively collected.Tumor HER2 protein expression was assessed by immunohistochemistry(IHC).Specimens with IHC 2+were further evaluated by fluorescence in situ hybridization(FISH)for gene amplification.HER2 status was classified as positive(IHC 3+),low expression(IHC 1+or IHC 2+/FISH-),and negative(IHC 0).The association between HER2-low expression and clinicopathological parameters,tumor-related biomarker expression,and patient prognosis was analyzed.Multivariate logistic regression was used to identify factors influencing HER2-low expression. Results:Among the 738 EGJA patients,259(35.1％)exhibited HER2-low expression.Univariate analysis showed that HER2-low expression was significantly associated with pathological N stage,TNM stage,Lauren classification,histological subtype and grade,mucinous phenotype,and programmed death-1(PD-1)expression(all P<0.05).No significant association was found with age,gender,vascular invasion,nerve invasion,T stage,or P53 and Ki-67 expression(all P>0.05).Multivariate logistic regression confirmed that moderate histological differentiation and mixed mucinous phenotype were independent factors associated with HER2-low expression(both P<0.05).Subgroup analysis of HER2-low cases revealed significant differences between IHC 1+and IHC 2+/FISH-groups in Lauren classification and histological subtype(both P<0.05),whereas other clinicopathological variables showed no significant differences(all P>0.05).Survival analysis indicated that overall survival differed significantly among patients with different Lauren classifications within(P=0.0196). Conclusion:HER2-low expression EGJA exhibits distinct clinicopathological characteristics and is closely associated with multiple pathological indicators and biomarker expression.Lauren classification may serve as an important reference for prognostic assessment in these patients.