ERCC1 And ERCC2 Expression In Esophageal Cancer And Gastric Cardiac Cancer: Correlation With Clinicopathologic Features And Prognosis

Objective: As the principal members of nucleotide excision repair system (NER) ,excision repair cross- complementing 1(ERCC1) is responsible for identifycation and incision at the 5'-side of the DNA lesion and is also involved in homologous recombination and interstrand cross-link repair, and excision repair cross-complementing 2(ERCC2) is a helicase belonging to the TFIIH complex, which participates in DNA unwinding. Both of them have been found not only expressed in normal tissue, but also in many solid tumor such as gastrointestinal cancer, non small-cell lung cancer and breast cancer. In lung cancer and ovarian cancer, ERCC1-positive patients couldn't derive a substantial benefit from adjuvant platinum-based chemotherapy, whereas in patients randomly assigned to the observation arm, ERCC1-positive patients had a better survival. However, its prognostic effect on malignant tumors in digestive system has been contradicted. Furthermore, the relationship of ERCC2 and prognosis of malignant tumors has been unclear.In this study, we investigated the expression of ERCC1, ERCC2 in human esophageal and gastric cardiac cancer by immunohistochemical staining, analyzed their correlation with the clinical pathological features, and their impact on prognosis in order to evaluate the feasibility as prognosis markers of esophageal and gastric cardiac cancer.Methods:1 Calculate minimum sample size in this study according to sample volume formula with enumeration data and get 80. Randomly select 137 cases of esophageal and gastric cardiac cancer who underwent surgical resection from January 1,2001 to December 31,2001 in the Fourth Hospital of Hebei Medical University. Patients who developed double cancer, received radiotherapy, or used non-platinum chemotherapeutics were dismissed. Register clinicopathologic features and follow up to December 31,2006. 108 patients were entered and 97 cases gained complete follow-up data. Build the Excel database about the patients'clinical data.2 Select 50 health esophageal and gastric cardiac tissue as control group. Detect the expression of ERCC1 and ERCC2 in esophageal and gastric cardiac cancer and normal tissue by S-P immunohistochemistry, and analyze their correlation with each other.3 Analyze the correlation of ERCC1, ERCC2 with clini- copathologic features and prognosis of esophageal and gastric cardiac cancer.Results:1 ERCC1 and ERCC2 expression in normal tissue and esophageal and gastric cardiac cancerThe positive expression of ERCC1 and ERCC2 in esophageal and gastric cardiac cancer were 38.1% and 24.7%, respectively. ERCC1 expression in cancer was higher than that in normal tissue, but there wasn't significant statistical difference between them (P>0.05), and ERCC2 expression in cancer was significantly higher than that in normal tissue (P<0.05). There was positive correlation between the expression of ERCC1 and ERCC2 ( Rs=0.238,P=0.019). 2 The correlation between expression of ERCC1, ERCC2 and clinical pathological features of esophageal and gastric cardiac cancerBoth ERCC1 and ERCC2 expression were significantly higher in well-differentiated cancer than those in moderately differentiated cancer and poor differentiation cancer (P<0.05). However, there wasn't significant statistical difference between moderately differentiated cancer and poor differentiation cancer(P>0.05). There were positive correlation between the both ERCC1 and ERCC2 expression and differentiation degree (Rs=0.284 , P=0.005; Rs=0.249 , P=0.014, respectively). Neither ERCC1 nor ERCC2 expression was correlated with sex, age, tumor location, length, depth, pathology type, lymph node metastasis or clinical stage.3 The correlation of ERCC1,ERCC2 expression with prognosis of esophageal and gastric cardiac cancer3.1 5-year survival rate of ERCC1-positive patients was 51.35%, which was higher than ERCC1-negative patients (26.67%). There was significant statistical difference between each other (P<0.05). ERCC1-positive patients have a better survival(P=0.014).3.2 5-year survival rate of ERCC2-positive patients was 50.00%, which was higher than ERCC2-negative patients (31.51%). There wasn't significant statistical difference between each other, but it was seemed that ERCC2-positive patients had a better survival than ERCC2-negative patients(P=0.070).3.3 Subset analyze between ERCC1,ERCC2 expression and the correlation with prognosis3.3.1 5-year survival rate of patients with groups of ERCC1, ERCC2 co-positive expression, single ERCC1-positive expres- sion, and single ERCC2-positive expression were 50.00%, 52.17%, 50.00%, respectively,which were significantly higher than patients with ERCC1,ERCC2 co-negative expre- ssion(22.00%) (P<0.05). There wasn't significant statistical difference between group of co-positive expression and group of single positive expression(P>0.05).3.3.2 In patients who received platinum-based chemotherapy, 5-year survival of groups of single positive expression, co-positive expression and co-negative expression were 38.10%, 27.27%, 44.44%, respectively. There wasn't signify- cant statistical difference among those three groups (P>0.05).3.3.3 There weren't significant statistical difference between 5-year survival rate of patients underwent adjuvant chemo- therapy and that of surgery alone(P>0.05). In group of positive expression(including single positive expression and co-positive expression), 5-year survival rate of patients with surgery alone was higher than patients with adjuvant chemotherapy. However, in group of co-negative expression, 5-year survival rate of patients with surgery alone was lower than patients with adjuvant chemotherapy.4 Depth of tumor invasion(P=0.024), number of lymph node metastasis (P=0.000), degree of differentiation(P=0.001) and clinical stage(P=0.000) were correlation with prognosis of esophageal and gastric cardiac cancer.Conclusion:1 ERCC1, ERCC2 were examined expression on different degree either in esophageal and gastric cardiac cancer or in normal tissue, and ERCC2 was higher expression in normal tissue than that in cancer.2 There were positive correlation between the both ERCC1 and ERCC2 expression and differentiation degree of esophageal and gastric cardiac cancer. As the differentiation degree grew better, the positive rate became higher. Furthermore, both ERCC1 and ERCC2 had positive correlation with each other.3 ERCC1 and/or ERCC2-positive expression patients had better prognosis than co-negative expression patients.