| Background and objective of the researchEsophageal carcinoma(EC)is a common upper gastrointestinal malignancy with morbidity and mortality at 9th and 6th place of global cancer,respectively.There are about 450,000 EC new cases worldwide each year,more than half of which occurs in China.Esophageal cell squamous carcinoma(ESCC)is the most common type in China.With the rapid development of molecular biology technology,more and more targeted drugs are used for cancer treatment,Human epidermal growth factor receptor 2(HER2)target drug,Herceptin,is the most common of targeted drugs.Herceptin for the treatment of patients with HER2-positive breast cancer,and has achieved good results.HER2 has also been discovered in ESCC,but the relationship between clinicopathological features of ESCC and prognosis is still controversial.In this study,95 ESCC cases were collected from June 2006 to July 2012 in the Second Affiliated Hospital of Zhengzhou University.Immunohistochemistry(IHC)and Fluorescence quantitative in situ hybridization(FISH)were used to detect the expression and amplification of HER2 in ESCC tissues.In order to provide reference for ESCC diagnosis and treatment,we will evaluate the relationship between HER2 expression and amplification and the clinicopathological features and prognosis of ESCC.Materials and methods 1 Study subjects95 ESCC cases were chosen from the Department of Pathology specimens’ database,the Second Affiliated Hospital of Zhengzhou University.These ESCC patients were not received radiotherapy and chemotherapy before surgery therapy.At the same time,65 cases of postoperative negative esophageal residual tissues were chosen as the control group.2 Experimental methodsThe expression and amplification of HER2 in ESCC samples were detected by IHC and FISH.3 Statistical methodsThe difference between the grade data was analyzed by Fisher’s or x~2 test.Survival analysis was performed using Kaplan-Meier survival curve and Cox proportional hazards model for single factor and multivariate analysis,P<0.05 was considered significantly statistical difference.Results 1 Characteristics of patientsA total of 95 ESCC patients were included in this study,with an average age of 62.9 ± 9.8 years,the gender ratio: 1.5:1.The middle and lower of tumor site(84.2%),tumor size<3cm(40.0%)and 3cm≥tumor size<5cm(42.1%),moderate and poor differentiation(88.4%),tumor infiltration to the muscular and fiber membrane(75.8%),and stage II and III of pTNM staging(73.7%)were the most common.In addition,20.0% of ESCC patients had a family history of cancer.A total of 65 cases of adjacent normal control,the average age of 63.4 ± 9.4 years,the gender ratio: 1.6:1.2 The association of HER2 overexpression and the clinicopathological features of ESCCHER2 overexpression was detected in 18.9%%(18/95)of ESCC tissues,with IHC 2+ of 13.7%(13/95)and IHC 3+ of 5.3%(5/95).In adjacent normal tissues,HER2 overexpression was discovered in 3.1%(2/65)of tissues,and 2 tissues all were IHC 2+.There was a significant difference between the two groups(x~2=12.496,P=0.002).There was no significant difference between HER2 overexpression and different age,sex,tumor location,tumor size,depth of invasion,distant metastasis and family history of cancer(P>0.05),but there was significant difference in the degree of differentiation,lymph node metastasis,and pTNM stage(P<0.05).3 The association of HER2 gene amplification and clinicopathological features of ESCCHER2 gene amplification was detected in 6.3%(6/95)of ESCC tissues,including 5(100%)of IHC 3+,and 1(7.7%)of IHC 2+.Spearman correlation analysis showed that the results of FISH test were positively correlated with the results of IHC test,the higher the HER2 gene amplification rate,the higher the HER2 protein expression rate(rs=0.549,P<0.001).There was no significant difference between HER2 gene amplification and different age,sex,tumor location,tumor size,depth of invasion,distant metastasis,and family history of cancer(P>0.05),but there was significant difference in different differentiation degree,lymph node metastasis,and pTNM staging(P<0.05).4 The association of HER2 overexpression and amplification and prognosis of ESCCThe prognosis of ESCC patients with HER2 overexpression was significantly poorer than those of negative expression(20.2vs.43.2 months),and there was a significantly statistical difference(x~2=5.221,P=0.022).Besides,ESCC patients with HER2 gene amplification patients had a poor prognosis(13.7vs.41.0 months),and there was a significantly statistical difference(x~2=4.498,P=0.034).The single factor analysis of Cox regression model showed that age,sex,tumor location,tumor size and family history of cancer had no effect on the overall survival of ESCC patients(P>0.05).The degree of differentiation,depth of invasion,lymph node metastasis,pTNM stage,HER2 overexpression and amplification were associated with poor prognosis in ESCC patients(P<0.05).In addition,the multivariate factor analysis of Cox regression model showed that HER2 overexpression and amplification were not independent risk factor for the prognosis of ESCC patients.ConclusionsThe overexpression or amplification of HER2 was obviously detected in ESCC tissues.The overexpression or amplification of HER2 is associated with tumor differentiation,lymph node metastasis,and pTNM staging.The ESCC patients with HER2 overexpression or amplification have poorer prognosis than those with negative expression or amplification. |
PDF Full Text Request