| Objective: The expression of human epidermal growth factor receptor 2(HER2)in gastric cancer(GC)has been reported worldwide,and data differed between countries and regions.The association with clinic-pathological features and prognosis remains uncertain.The present study was aimed to investigate the expression of HER2 in patients with gastric cancer in northern China,and to analysis the efficacy of trastuzumab in patients with HER2-positive advanced gastric cancer.Methods: A total of 492 Patients with pathologically-proven gastric cancers was retrospectively analyzed for HER2 status by immunohistochemistry(IHC).Fluorescence in situ hybridization(FISH)analysis was used in 61 GCs cases to assess HER2 gene amplification.All Patient clinic-pathological parameters data and survival information were collected.Univariate and multivariate relationship between HER2 positive rate and clinicopathological variables was determined using a binary logistic regression.Twentyseven patients with HER2-positive advanced gastric cancer were divided into two groups according to the first-line treatment,trastuzumab + chemotherapy and chemotherapy group.The differences in overall survival(OS),progression free survival(PFS),objective response rate(ORR),and disease control rate(DCR)were analyzed.Survival analysis was performed using Kaplan-Meier curves and log-rank tests.The chi-square test was used to compare the baseline characteristics and rates between groups.Results: 492 patients were tested for HER2 protein expression by Immunohistochemistry(IHC).A total of 50 patients were HER2 positive.There were 38 patients with HER2 IHC2+ who did not undergo further FISH testing,so the HER2 status was unknown.The positive rate of HER2 was 11.0%(50/454).As for the 61 cases analyzed by FISH,2(of 2,100.0%)HER2 IHC 3+ cases,16(of 52,30.8%)IHC 2+ cases,and 1(of 7,14.3%)IHC 1+/0 cases showed HER2 gene amplification.Univariate Logistic Regression Analysis showed that HER2 positive was more frequently observed in male(P=0.048),age ≥ 60 years old(P=0.023),cardia tumor(p<0.001),well or moderately differentiated type(p=0.004),T1-T2 stage(p<0.001)and N2-N3 Lymph node metastasis(N2,p=0.011;N3,p=0.011);Multivariate Logistic Regression Analysis showed that HER2 positive rate was associated with the following clinicopathological factors: age ≥60 years old(p=0.050),well or moderately differentiated type(p =0.001);tumor located on the cardia(p < 0.001);T1-T2 stage(p < 0.001);N2-N3 lymph node metastasis(N2,p=0.019;N3,p=0.001).The median survival time of HER2-positive patients and HER2-negative patients in the general population(stage I-IV)was 30.2 months and 34.4 months,respectively,P=0.381.The median survival time of HER2 positive and negative patients with stage I-III gastric cancer was 39.0 months and 51.4 months,respectively(p=0.051).Among patients with stage IV,there was no significant difference in survival between HER2 positive patients and HER2 negative patients(12.0 months vs.10.5 months,p=0.385);In the patients with stage II and III,the median survival time was significantly shorter in HER2 positive patients than that of HER2 negative patients(stage II,51.8 months vs.64.7 months,p=0.006;stage III,27.8 months vs.37.7 months,p=0.038).In patients with HER2-positive advanced gastric cancer,the median overall survival was 13.2 months in patients treated with trastuzumab + chemotherapy,and 11.3 months in chemotherapy group(p=0.311).The median progression-free survival was 7.0 months and 6.0 months,respectively(p=0.025).The ORR of the two groups were 31.3% and 18.2%,respectively(p=0.662),and the DCR were 93.8% and 54.5%,respectively(p=0.027).Conclusions: Approximately 11.0% of Patients in northern China with primary gastric cancer(GC)were HER2-positive;HER2 overexpression was more common in patients with ≥60 years of age,well or moderately differentiated carcinomas,T1-T2 stage,multiple lymph node metastases,and Cardia tumor.HER2 positive rates were not correlated with specimen source or TNM stage.HER2 expression was associated with poor prognosis of stage II and III gastric cancer,and was not associated with the prognosis of stage IV gastric cancer.Trastuzumab plus chemotherapy demonstrated anti-tumor activity in the first-line treatment in patients with HER2-positive advanced gastric cancer.Compared with chemotherapy alone,the combinational therapy improved PFS significantly,and showed a trend of OS prolonging. |
