Overexpression Of Human Epidermal Growth Factor Receptor2Assoclated With The Progression Of Esophageal Patients

Background&Objective:As a common gastrointestinal malignancy, the incidence and mortality of esophageal cancer remain high. And China is one of the high-risk areas all around the world. Recently along with the rapid development of molecular biology, the researchers not only have done plentiful basic and clinical research for the occurrence, development, diagnosis and treatment of esophageal cancer, but also have made certain progress. However, the survival rate for5years after esophagectomy is still less than20%at home and abroad.The occurrence and development of esophageal cancer involved the joint action of abnormal changes of multiple genes and mechanism of molecular biology with accumulated process gradually.As the second member of epidermal growth factor receptor family, human epidermal-growth-factor receptor2, participated in the signal transduction of tyrosinase and promoted cell proliferation, belongs to a kind of transmembrane glycoprotein with tyrosinase activity. The original cancer gene Her-2was first discovered as a new cancer gene from neuroblastoma by Shih in1981, named for neu. Later large foundation and pathology researches showed that her-2expressed less or negatively in the normal tissue, but high expressed in variety of tumor, which related with the poor prognosis of tumor. The research about her-2’s expression and meaning in the tissue of esophageal cancer is still less at present. In order to investigate the roles of her-2occurred in the process of the development of esophageal cancer, this study aims to test the expression level of her-2in the tissue of esophageal cancer, and the relationship with the clinical and pathological features of the patients with esophageal cancer, and the influence to the prognosis. Methods:72esophageal cancer tissues were obtained from patients who underwent esophageal cancer Ro resection in Provincial Hospital affiliated to Shandong University.15normal esophageal tissues were obtained from the region of5cm farther to the cancer or the tissue edge as control group. All of the patients were under Initial Treatment, underwent no other adjuvant treatments, such as chemotherapy, radiotherapy and biotherapy before the surgery, in order to eliminate their effects on gene expression. All87specimens were examined by immunohistochemistry to detect the expression of her-2protein. Input all data to SPSS software to establish a database to analysis. The chi-square test was used to compare the expression of her-2protein in groups with different clinical pathological characteristics. Kaplan-Meier method was performed to estimate the5-year survival rate. Compare the survival between different her-2expression groups by using Log-rank test. Investigate the independent prognostic factors of esophageal cancer by Cox regression multivariate analysis. Results:Immunohistochemical results showed that20(27.8%) of72esophageal cancer tissues high expressed her-2protein, while52esophageal cancer tissues low expressed her-2protein. All15normal esophageal tissues low expressed her-2protein. And there was a significant difference between two groups (P<0.05).3(8.6%) of35esophageal cancer tissues with well-differentiated or moderately differentiated high expressed her-2protein, while17(46.0%) of37esophageal cancer tissues with poorly differentiated high expressed her-2protein. Compared the her-2expression between two groups by χ2test, there was a significant difference (continuity correction χ2=10.730, P<0.01). None high expressed her-2protein in4esophageal cancer tissues infiltrated to the mucosa and submucosa, and2(7.4%) of27esophageal cancer tissues infiltrated to muscularis high expressed her-2protein, while18(43.9%) of41esophageal cancer tissues infiltrated to adventitia high expressed her-2protein. Compared the her-2expression between three groups by Fisher’s exact test, there was a significant difference (χ2=12.196, P<0.01).10(18.5%) of54esophageal cancer tissues without lymph node metastasis high expressed her-2protein, while10(55.6%) of18esophageal cancer tissues with lymph node metastasis high expressed her-2protein. Compared the her-2expression between two groups by χ2test, there was a significant difference (χ2=9.231, P<0.01).1(4.5%) of22esophageal cancer tissues with stage Ⅰ high expressed her-2protein, and11(35.5%) of31esophageal cancer tissues with stage Ⅱ high expressed her-2protein while8(42.1%) of19esophageal cancer tissues with stage III high expressed her-2protein. Compared the her-2expression between different clilial stage groups by Fisher’s exact test, there was a significant difference between three groups (χ2=9.751, P<0.01). However, nosignificant correlations with gender, age, location, tissue typing and family history were demonstrated for her-2expression. The overall5-year survival rate of these esophageal cancer patients is27.8%. Furthermore, the5-year survival rate in patients with high expression of her-2protein was significantly lower than those with low expression(5.0%vs36.5%, χ2=31-936, P<0.001). The results of Cox regression single factor analysis showed that differentiation degree, Infiltration depth, pTNM stage, and her-2protein expression were significant influence factors of the overall5-year survival in esophageal cancer patients(P<0.05). The results of Cox regression multivariate analysis confirmed that differentiation degree (RR=3.146, P=0.001), Infiltration depth (RR=2.839, P=0.010), pTNM stage (RR=2.117,P=0.002), and her-2protein expression (RR=2.192, P=0.025) were independent prognostic factors.Conclusions:This study tested the expression of her-2protein in esophageal cancer tissues by immunohistochemistry, which found that the expression of her-2protein in esophageal cancer tissues is higher than those in adjacent normal esophageal tissues. This shows that her-2, as a kind of potential cancer-causing genes, may play an important function in the development of esophageal cancer by raising its expression. The expression of her-2is closely related to differentiation degree, infiltration depth, lymph nodes’ metastasis and pTNM stage of the esophageal cancer. The lower level of its differentiation, the deeper infiltration depth, the higher clinical stage and with lymph nodes’metastasis may generate the higher expression of her-2protein. However, no significant correlations with gender, age, location, tissue typing and family history were demonstrated for her-2expression. The relationship between her-2protein expression in esophageal cancer and the prognosis of patients suggested that the5-year survival rate of patients with high her-2expression is significantly lower than the patients with low her-2expression. Besides the influence of differentiation degree, infiltration depth, lymph node metastasis and pTNM stage to the prognosis, the level of her-2expression is also an independent prognostic factor in esophageal cancer patients. Her-2might become a potential molecular marker of diagnosis and new targets of clinical treatment of esophageal cancer.