Expression And Clinical Significance Of EGFR,HER2 And HER3 In Mongolian Esophageal Squamous Cell Carcinoma Tissues

Objective: To explore the expressions of epidermal growth factor receptor(EGFR),epidermal growth factor receptor 2(HER2)and epidermal growth factor receptor3(HER3)in esophageal squamous cell carcinoma(ESCC)of Mongolian patients and their correlation with common clinicopathological features and postoperative survival time.To provide a reference point for postoperative evaluation of esophageal squamous cell carcinoma(ESCC).The correlation between the expression of EGFR and the expression of HER2 and HER3 in esophageal squamous cell carcinoma tissues of Mongolian patients was also analyzed.Methods: The postoperative paraffin-embedded specimens of 72 patients with esophageal squamous cell carcinoma who underwent surgical treatment in the First Affiliated Hospital of Inner Mongolia Minzu University from September 2016 to September 2021 were collected,and the paraffin-embedded specimens of 72 normal esophageal tissues adjacent to cancer of the same patients were collected as controls.Immunohistochemistry(IHC)staining was used to detect the protein expression of EGFR,HER2 and HER3 in 72 ESCC tissues and adjacent normal esophageal tissues.The common clinicopathological data of the patients were collected,and the postoperative follow-up was conducted.SPSS23.0 software was used for data screening,sorting and statistics.X2 was used to analyze the expression of EGFR,HER2 and HER3 proteins in cancer tissues and their relationship with common clinicopathological data of ESCC.Log-rank test and Cox proportional hazards model were used to analyze the relationship between the expression of EGFR,HER2,HER3 and the two-year survival rate of patients with esophageal squamous cell carcinoma(ESCC),and Kaplan-Meier survival curve was drawn.The correlation between EGFR expression and HER3 expression was analyzed by column linkage number correlation.Results :(1)the positive expression rate of EGFR was 55/72(76.39%),HER2 was 1/72(1.39%)and HER3 was 14/72(19.44%)in 72 paraffin-embedded esophageal squamous cell carcinoma specimens.The positive expression rate of EGFR,HER2 and HER3 in normal esophageal tissues adjacent to ESCC was 2/72(2.78%),0/72(0.00%)and 3/72(4.17%),respectively.The data showed that:(1)The expressions of EGFR and HER3 in 72 Mongolian patients with esophageal squamous cell carcinoma(ESCC)were higher than those in adjacent normal esophageal tissues,and the differences were statistically significant(P < 0.05).(2)The expression of HER2 in 72 Mongolian patients with esophageal squamous cell carcinoma(ESCC)was higher than that in adjacent normal esophageal tissues,but the difference was not statistically significant.(2)Clinicopathological characteristics analysis showed that:(1)EGFR positive expression was significantly correlated with tumor differentiation(X2= 4.451 A,P=0.048).Such as gender(X2=0.175a),age(X2=0.167a),depth of tumor invasion(X2= 0.404A),tumor size(X2=0.13a),TNM stage(X2= 0.02A),vascular invasion(X2=0.200a),nerve invasion(X2= 0.409A),lymph node metastasis(X2= 0.409A).X2= 0.007A),and the differences were not statistically significant(P > 0.05).(2)HER3 expression in ESCC was significantly correlated with the depth of tumor invasion(X2= 4.080 A,P=0.043).Compared with age(X2=0.686a),gender(X2=1.580a),tumor size(X2)=2.384a),TNM stage(X2=0.010a),tumor differentiation(X2=0.071a),lymph node metastasis(X2=0.150A),vascular invasion(X2=0.349 A),nerve invasion(X2=0.290a)and so on,there was no significant correlation(P > 0.05).(3)Log-rank univariate analysis showed that:(1)The 2-year survival rate of patients with EGFR-positive esophageal squamous cell carcinoma was 34.5%,with an average survival time of 15.264 months,while the 2-year survival rate of patients with EGFR-negative esophageal squamous cell carcinoma was 76.9%,with an average survival time of 20.692 months.The 2-year survival rate and mean survival time of patients with EGFR positive expression were significantly lower than those with EGFR negative expression(log-rank X2=5.904,P=0.015).(2)The 2-year survival rate of patients with HER3-positive ESCC was 22.7%,with a mean survival time of 13.060 months.The 2-year survival rate of patients with HER3-negative ESCC was 57.5%,with a mean survival time of 18.610 months.The 2-year survival rate and mean survival time of patients with HER3 positive expression were significantly lower than those with HER3 negative expression(log-rank X2=8.709,P=0.003).(3)The 2-year survival rate of patients with deep invasive T1 esophageal squamous cell carcinoma was57.1%,and the average survival time was 18.444 months.The 2-year survival rate of patients with invasive depth T2 esophageal squamous cell carcinoma was 66.7%,and the mean survival time was 16.071 months.The 2-year survival rate of patients with deep invasive stage T3 esophageal squamous cell carcinoma was 25.7%,and the mean survival time was 15.312 months.The 2-year survival rate and mean survival time of T3 stage were lower than those of T1 stage(log-rank X2=6.252,P=0.044).(4)The 2-year survival rate of patients with esophageal squamous cell carcinoma in poorly differentiated group was23.8%,and the average survival time was 14.685 months.The 2-year survival rate of patients with esophageal squamous cell carcinoma in the middle differentiation group was47.1% and the average survival time was 15.176 months.The 2-year survival rate of patients with esophageal squamous cell carcinoma in well-differentiated group was 81.3%,and the average survival time was 21.188.The 2-year survival rate and mean survival time of the poorly differentiated group were lower than those of the moderately differentiated and well-differentiated groups(log-rank X2=10.930,P=0.004).(5)The 2-year survival rate of esophageal squamous cell carcinoma with lymph node metastasis was 34.1%,and the average survival time was 15.091 months.The 2-year survival rate was 61.9% and the mean survival time was 19.048 months.The 2-year survival rate and mean survival time of the lymph node metastasis group were lower than those of the lymph node non-metastasis group(log-rank X2=4.221,P=0.040).(6)Other clinicopathological data had no significant effect on the 2-year survival rate of patients with esophageal squamous cell carcinoma(P >0.05).(4)The significant variables in univariate analysis were included in COX regression model for multivariate analysis.The results showed that:(1)the risk of death in EGFR-positive patients was 3.858 times that in EGFR-negative patients;(2)The risk of death in HER3-positive patients was 1.959 times that in HER3-negative patients;(3)The risk of death in patients with differentiated tumors was 3.987 times that in patients with well-differentiated tumors,and the risk of death in patients with poorly differentiated tumors was 4.244 times that in patients with well-differentiated tumors.(5)The correlation between EGFR and HER3 was analyzed by column linkage number.The number of links between EGFR and HER3 was 0.347,P<0.05,indicating a statistical difference.EGFR expression was positively correlated with HER3 expression.Conclusions :(1)EGFR and HER3 are highly expressed in Mongolian esophageal squamous cell carcinoma(ESCC)tissues,and there is statistical significance.(2)The role of HER2 in Mongolian esophageal squamous cell carcinoma remains unclear.(3)The positive expression of EGFR and HER3 may be closely related to the poor prognosis of ESCC.(4)The expression of EGFR was positively correlated with the expression of HER3 in esophageal squamous cell carcinoma(P < 0.05).