Expression And Clinicopathological Significance Of C-erbB-2, CEA, P53, E-cadherin, Ki-67 And Bax In Gastric Adenocarcinoma

Objective:To explore new molecular markers as prognostic indicators for gastric adenocarcinoma, we investigated the expression of c-erbB-2, CEA, p53, E-cadherin, Ki-67 and Bax in gastric adenocarcinoma and analyzed the relationships between their expression and clinicopathological features as well as postoperative survival.Methods:All tissues investigated in this study were obtained from patients (n = 150) who had underwent gastrectomy between 2002 and 2003 in Jiangxi Province People's Hospital. Both 150 cases of gastric adenocarcinoma tissues and 18 cases of non-cancerous tissues were made into 4 tissue microarrays. Expression of c-erbB-2, CEA, p53, E-cadherin, Ki-67 and Bax in the tissue microarrays were detected by PV-6000 two-step immunohistochemical method. The relationships between their expression and clinicopathological features as well as postoperative survival in 74 of 150 patients with gastric adenocarcinoma who were followed up successfully were studied. Chi-square and Fisher exact probability tests, non-parametric Spearman rank correlation analysis were used to analyz the relationships between the clinical and immunohistochemical variables and the markers. Univariate survival analysis applies Kaplan-Meier method and Log-Rank test to calculate and compare the cumulative survival rate and postoperative mean survival time in 74 patients with gastric adenocarcinoma. COX proportional hazards regression model was used for multivariate survival analysis.Results:(1) The positive expression rates of c-erbB-2, CEA, p53, E-cadherin, Ki-67 and Bax in 150 cases of gastric adenocarcinoma specimens were 7.3%(11/150), 29.3%(44/150), 50.0%(50/150), 87.3%(131/150), 61.3%(92/150) and 40.0%(60/150), respectively. In non-cancerous tissues, c-erbB-2, CEA and p53 didn't express, and the positive expression rates of E-cadherin, Ki-67 and Bax were 94.4%(17/18), 33.3%(6/18) and 11.1%(2/18), respectively. Expression of CEA, p53, Ki-67 and Bax in gastric adenocarcinoma were higher than in non-cancerous tissues(p<0.05), but expression of c-erbB-2, E-cadherin had no differences in gastric adenocarcinoma and non-cancer tissues(p>0.05).(2) Non-parametric Spearman rank correlation analysis showed that: there was a positive correlation with p53, Bax and Ki-67 (r = 0.293, 0.317, respectively, p<0.05); while there were no correlations between the other proteins (p>0.05) .(3) Expression of c-erbB-2 were related to the histologic type, degree of differentiation and Laurén's classification. Expression of CEA were associated with histologic type and distant metastasis. Expression of p53 in gastric adnocarcinoma were correlated with sex, Bormann's classification and depth of invasion. Expression of E-cadherin were related to histologic type. Expression of Ki-67 were correlated with sex, histologic type, Bormann's classification and depth of invasion. Expression of Bax were associated with tumor location and depth of invasion. (4) Postoperative survival in 74 patients with gastric adenocarcinoma showed that: 1-, 3-, and 5-year survival rates in 74 patients with gastric adenocarcinoma were 83.8%(62/74), 70.3%(52/74) and 63.5%(47/74), respectively.(5) Univariate survival analysis demonstrated that: There were significant differences in postoperative survival time according to age, Bormann's classification, degree of differentiation, Laurén's types, depth of invasion, lymph node metastasis, resection margin involvement, pTNM staging, respectively. There were shorter survival time in patients with age≥50, Bormann type III/IV, poor differentiation, diffuse type, serosal layer invasion, lymph node metastasis, resection margin involvement, pTNM stage III/IV than age<50, Bormann type 0/I/II, well/moderate differentiation, intestinal type, myometrial invasion, without lymph node metastasis, resection margin not involved, pTNM stage I/II(p<0.05). But there were no significant differences in survival time according to proteins expression of c-erbB-2, CEA, p53, E-cadherin, Ki-67 and Bax, sex, tumor location and size, histologic classification and distant metastasis. Further analysis of proteins co-expression showed that: In the CEA-negative group, postoperative mean survival time in patients with c-erbB-2 positive was shorter than c-erbB-2-negative patients. In the c-erbB-2 negative, p53 negative and Ki-67 negative groups, respectively, postoperative mean survival time in patients with CEA positive was lower than patients with CEA negative. And in the Ki-67-negative group, postoperative mean survival time in Bax-positive patients shorter than Bax-negative patients. There were significant differences in the proteins co-expression of c-erbB-2, CEA, Ki-67 and Bax, while the other proteins co-expression groups were not found to be statistically significant.(6) COX multivariate regression model showed that: CEA, age, lymph node metastasis and resection margin involvment are the independent prognostic factors influencing prognosis of postoperative patients with gastric adenocarcinoma.Conclusions:(1) There are a certain degree of correlations between proteins expression of c-erbB-2, CEA, p53, E-cadherin, Ki-67, Bax in gastric adenocarcinoma and clinicopathological features. ( 2 ) c-erbB-2, CEA, Ki-67, Bax proteins co-expression are associated with shorter survival time in patients with gastric adenocarcinoma, suggesting that combined detection of the c-erbB-2, CEA, Ki-67 and Bax proteins may determine the prognosis of patients with gastric adenocarcinoma.