Actication Of Src Kinase In Gastric Cancer:an Indicton Of Clinical Prognosis And Its Correlationship With The Expression Of HER2and Ki67

Objective:c-Src activity in gastric carcinoma was measured to assess whether it is a biomarker of clinical prognosis and whether it correlate with HER2/KJ67expression and other clinical parameters.Methods:(1)123of radically surgical reseciton specimens and56of corresponding adjacent specimens were collected at Lishui Center Hospital and the First Affiliated Hospital of Medical College of Zhejiang University, from January2008to December2010. All of the patients were follow-up.(2) Immunohistochemical investigations were carried out to study of the expression of HER2, p-Src(Y419), Ki67proteins respectively in the gastric cancer specimen and corresponding adjacent specimens. The relationship of expression of p-Src(Y419) with clinicopathologic variables and the interrelationship of the expression of HER2, p-Src(Y419) and Ki67were analyzed. The continuous variable and ranked datum were tested by rank test; The grouped datum were tested by chisquare test. The interrelationships of the three proteins were tested by Spearman’s rank correlations and curve fit. Univariate survival analysis was carried out using Kaplan-Meier plots and the log rank test. Univariate two years survival analysis was carried out using chisquare test. Two years survival multivariate analysis was performed using binary logistic regression.The SPSS16.0statistical analysis software was used for data analysis.Results:(1) The expression of HER2、p-Src (Y419)、Ki67proteins in the gastric cancer tissues were higher than the adjacent nontumorous tissues which is significant(P<0.05).(2) P-Src (Y419) staining intensity was associated with tumor size, the extent of tumor differentiation and Lauren type (P<0.05). P-Src (Y419) staining extent and the multiplying scores of the extent and intensity of p-Src (Y419) staining were all associated with tumor size, the extent of tumor differentiation, pT and pTNM classification.(3)Univariate survival analysis showed a significant association between overall survival time and p-Src (Y419) staining intensity, p-Src (Y419) staining extent and the multiplying scores of the extent and intensity of p-Src (Y419). Multivariate analysis revealed that elevated p-Src (Y419) staining intensity was an independent poorly prognostic parameter for two-years survival time.(4) There were positive correlation of HER2, Ki67with p-Src (Y419) staining extent, intensity and the multiplying scores of the extent and intensity of p-Src (Y419) staining, respectively. There was positive correlation of HER2expression between Ki67expression (P<0.05).Conclusion:The specific activity of the non-receptor protein tyrosine kinase, c-Src, is increased in the gastric adenocarcinomas compared to adjacent mucosa. Increased Src activity significantly correlated with tumor, the extent of differentiation, Lauren type, pT and pTNM classification. Src activity is an independent indicator of poor clinical prognosis in all stages of human gastric carcinoma, which show that Src-specific inhibitors may have a therapeutic role in inhibiting tumor progression and metastasis. The interrelationship of the expression of HER2, p-Src(Y419) and Ki67proteins were significantly positive, which shows that HER2-Src signaling pathway maybe make an important role in the progression of gastric carcinoma.