Objective To investigate the expression and prognostic significance of human epidermal growth factor receptor 2(EGFR 2,also called HER2 or c-ErbB2)in elderly intracranial meningio-mas.Methods A total of 52 elderly patients with intracranial meningioma who underwent surgi-cal resection in our department from February 2021 to January 2023 were consecutively recruited in this study.According to the World Health Organization(WHO)classification,40 cases were as-signed into WHO grade Ⅰ and 12 cases into WHO grade Ⅱ/Ⅲ.Based on the phosphorylation level of HER2(p-HER2),there were 39 cases with low p-HER2 expression and 13 cases with high expression.The expression of HER2 extracellular domain(ECD),intracellular domain(ICD)and phosphorylated receptor(6B12)were detected by immunohistochemistry.Double probe fluores-cence in situ hybridization(FISH)was used to detect the amplification of HER2.Time to recur-rence(TTR)and overall survival(OS)were recorded during follow-up.Cox proportional hazards regression model and Kaplan-Meier survival curve were employed to analyze the relationship of HER2 expression and recurrence and death risk in these patients.Results The positive rate of ICD-CB11 and ICD-3B5 was both 100％,while that of ECD-SP3 and 6B12(p-HER2)was 61.54％(32/52)and 25.00％(13/52),respectively in the elderly patients.In normal meningeal tissues,negative results were observed in all above four antibody immune responses.In addition,there was no significant difference in HER2 expression between WHO group 1 and WHO group Ⅱ/Ⅲ(P＞0.05).HER2 gene amplification was not detected in all elderly patients with meningioma,and the ratio of HER2 to CEP17 signals was 1.09±0.11,ranging from 0.84 to 1.35.Univariate and multivariate COX proportional hazard regression analysis showed that high expression of p-HER2 was an independent risk factor for recurrence and death in elderly patients with meningioma(P＜0.05).During follow-up,the patients with low p-HER2 expression had higher relapse-free survival rate and longer median recurrence-free survival(RFS)when compared with the patients with high p-HER2 expression(74.36％vs 30.77％,1.66 year vs 0.56 year,P log rank＜0.01).Survival analysis indicated that higher total survival rate and longer median OS were observed in the patients with low p-HER2 expression than those with high p-HER2 expression(82.05％vs 46.15％,2.27 year vs 0.58 year,Plogrank＜0.01).Conclusion HER2 is overexpressed in elderly patients with intracra-nial meningioma,and p-HER2 overexpression is associated with an increased risk of recurrence and death.HER2 may be used as a prognostic tool in elderly patients with meningioma,and is ex-pected to be a potential therapeutic target.