Her-2 Expression Of Advanced Gastric Carcinoma And Its Correlation With Clinicopathologic And Prognosis

Objective: Gastric carcinoma ranks the second among any malignant tumors in terms of morbidity and mortality. As molecular biology progresses, the Her-2 gene has been suggested to be associated with the development, progression and prognosis of gastric carcinoma, and the therapies targeting at Her-2-positive progressive gastric carcinoma could extend patient survival. This paper investigates the correlation between the Her-2 expression status and the clinical pathological features and prognosis in patients with progressive gastric carcinoma, in an attempt to provide an individual therapeutic option for gastric carcinoma.Materials and methods: 616 patients pathologically confirmed with gastric carcinoma in Fujian Medical University Union Hospital in January 2013 to December 2014 were selected as the subjects. All the tissue specimens(including gastroscopic biopsy and surgical resection specimens) were tested for the Her-2expression status using the immunohistochemistry(IHC)method, some patients detected as Her-2(2+) combined with FISH examine,and those detected as Her-2( 3+) and Her-2(2+) with FISH examine resulted in gene amplification were assigned to the over-expression group for analysis of the Her-2 over-expression status in our hospital. 123 patients with progressive gastric carcinoma with complete clinical and pathological data with contact information were included in survival follow-up for analysis of the association between Her-2 over-expression and the pathological features and prognosis of progressive gastric carcinoma.Based on Her-2 expression and whether postoperative chemotherapy and target therapy was received, the 123 patients with progressive gastric carcinoma were assigned to different groups, for analysis of the association between Her-2expression, target therapy and chemotherapy and the prognosis of gastric carcinoma.Results:1. When detecting the Her-2 expression status using the IHC method for the 616 patients with gastric carcinoma in our hospital, 395( 64.12%) patients were detected as Her-2(0), 115(18.67%) patients were detected as Her-2(1+), 56(9.09%) patients were detected as Her-2(2+), 50(8.12%) patients were detected as Her-2(3+), 27 of 56 patients detected as Her-2(2+) combined with FISH examine,5 patients resulted in gene amplification,and those detected as Her-2(3+)and Her-2(2+) with FISH examine resulted in gene amplification were assigned to the over-expression group, contributing to an 8.93% Her-2over-expression rate in our hospital.2. Among the 123 patients,Tumor location and Lauren's type are correlated with Her-2 over-expression; specifically, the Her-2 over-expression rate was 36.36% in carcinoma of gastroesophageal junction(carcinoma of gastric cardia), which was higher than in any other sites(X2=9.53,P<0.05). The Her-2 over-expression rate was 29.29% in intestinal type gastric carcinoma, which was higher than in diffuse and mixed types, with statistically significant differences(X2=7.54,P<0.05). The pathological features such as gender, age, TNM stage, tumor size, histological type,serosa infiltration, lymph node metastasis, vascular invasion, perineural invasion,CEA, CA199 and CA125 were not noted to be correlated with Her-2over-expression.3. Among the 123 patients, 24 with Her-2 over-expression had the median survival18.09�1.35 months, and 99 negative for Her-2 had the median survival 20.92�0.74 months, indicating shorter survival in patients with Her-2 over-expression than in patients negative for Her-2,with statistically significant difference(X2=4.07,P=0.04< 0.05). Specifically, 4 of the patients with Her-2 over-expression treated with trastuzumab were alive at the end of follow-up period, had the median survival over 24 months;20 of the patients with Her-2 over-expression not treated with trastuzumab had the median survival 17.35�1.44 months, indicating shorter survival than in patients negative for Her-2, with statistically significant difference(X2=5.98,P=0.01<0.05).4. Among the 123 patients, 90 receiving postoperative chemotherapy had themedian survival 21.27�0.78 months, while the 33 patients not receiving postoperative chemotherapy had the median survival 18.02�1.17 months,indicating survival benefit associated with postoperative chemotherapy, with statistically significant difference(X2=5.35, P=0.02<0.05). Among the patients negative for Her-2, 72 receiving postoperative chemotherapy had the median survival 21.83�0.86 months, and 27 not receiving postoperative chemotherapy had the median survival 18.47�1.38 months, indicating survival benefit associated with postoperative chemotherapy for patients with Her-2-negative progression gastric carcinoma(X2=4.14,P=0.04<0.05). Among the patients with Her-2over-expression, 19 receiving postoperative chemotherapy had the median survival18.91�1.62 months, and 5 not receiving postoperative chemotherapy had the median survival 15.20�1.77 months, indicating no statistically significant difference between the two groups(X2=2.26,P=0.13>0.05).5. For the prognosis of survival analysis identified perineural invasion as an important influencing factor for the prognosis of gastric carcinoma.Conclusions: 1. In progressive gastric carcinoma, Her-2 over-expression is correlated with the tumor location and Lauren's type, with higher Her-2over-expression rates in carcinoma of gastroesophageal junction and intestinal type gastric carcinoma. 2. Her-2 over-expression is predictive of poor prognosis in progressive gastric carcinoma. 3. Postoperative chemotherapy could result in survival benefit for patients with progressive gastric carcinoma. 4. perineural invasion is an important prognostic factor for gastric carcinoma.