The Significance Of Combined Detection Of HER-2 Gene Amplification And K-RAS Gene Mutations In Gastric Carcinoma

BackgroundGastric cancer is a common malignant tumor.Annual new patients with gastric carcinoma in the world are more than 930,000,and those in our country occupy 60%.The morbidity and the mortality are more than twice of the average around the world.Its morbidity shows an upward and younger trend.In recent years,the morbidity of gastric cancer in young people has doubled that of 1980 s.Surgical removal is the primary therapy method,and patients with early gastric carcinoma can be cured by surgery.But most patients with gastric cancer have reached middle and advanced stage at the time of diagnosis.Even adopting the comprehensive treatment centered by surgery,chemotherapy,radiotherapy and hormonotherapy can achieve the poor effect.Five-year survival rate is less than 20%.Thus,finding new therapy pathway,for example molecular targeting treatment,becomes the hot issue of study on gastric cancer.Human epithelial growth factor receptor 2(HER-2)is over expression in gastric carcinoma,closely related to the prognosis of gastric carcinoma,which can guide the molecular targeting treatment of gastric carcinoma.In gastric carcinoma,the mutation rate of K-RAS gene is 9%.The mutation of K-RAS causes MAPK pathway independent of structural activation of EGFR,so as to influence the curative effect of cetuximab.HER-2 gene is more studied on gastric carcinomar,and K-RAS gene is more studied on colorectal carcinoma.But studies on gastric carcinoma are few to report.Research has shown that the development of colorectal cancer is related to synergistic effect of HER-2 and K-RAS.Then in the occurrence and development of gastric carcinoma,are the two related or not? Therefore,this paper,through exploring whether there is a relationship between the gene amplification of HER-2 and the gene mutation of K-RAS in gastric carcinoma,understands the target of anti-tumor drug treatment,to provide better help for target anti-tumor drug treatment of gastric carcinoma.ObjectiveTo explore the relationship between the protein expression and gene amplification of HER-2 in gastric carcinoma,as well as the significance between the gene amplification of HER-2 and the gene mutation of K-RAS.Methods67 cases of gastric carcinoma specimens were collected,which are radically cured by surgical resection in the pathology department in No.150 Hospital of PLA from June 2013 to October 2015.Fresh specimens were fixed in 10% neutral formalin,respectively making routine HE staining,immumohistochemical staining(IHC),fluorescence in situ hybridization(FISH),and the detection of gene sequencing.Results1.The positive expression of HER-2 protein is localized on cell membrane,and the rate of positive expression is 40.3%(27/67).Its expression rate shows significant differences from the infiltration depth of gastric cancer(P<0.05)and lymphatic metastasis(P<0.05),but no significant differences from the gender(P>0.05),onset age(P>0.05),and histological type(P>0.05).2.The expression of HER-2 protein is 40.3%(27/67),and those who with positive 3+ of HER-2 occupy 9%(6/67).Those who with 2+ of HER-2 protein is 13.4%(9/67).Those who with 1+ of HER-2 protein is 17.9%(12/67).Gene amplification rate of HER-2 detected by FISH is 18.5%(5/27).Those who with HER-2 gene copy number increasing and gene amplification are totally 48.1%(13/27).Conclusion3.K-RAS gene mutation is quantitatively determined as 7.5%(5/67),which are all mutation of 12 codon of K-RAS.Among them,2 cases are mutation of low kurtosis lower than 10%,and 3 cases are mutation of high kurtosis higher than 10%(Mutation numerals are respectively: 17,29,and 30).Except one case is GGT-GAT mutant type,others are all GGT-GTT mutant type.In the 5 cases of K-RAS gene mutation in this group,except one case has both gene mutation of K-RAS and gene amplification of HER-2,other four cases are all without gene amplification of HER-2.Conclusions1.Protein expression ratio of HER-2 has positive relation with invasion depth of gastric carcinoma and lymphatic metastasis.The protein expression and gene amplification of HER-2 has highly consistent.Detecting protein expression of HER-2 by immunohistochemical method can be a screening means of clinical treatment.Patients with HER-2 protein expression(2+)should routinely make fluorescence in situ hybridization.2.The detection of HER-2 in gastric carcinoma has strong heterogeneity.The detection specification and refinement of HER-2 is the guarantee of correct guiding pharmacy.This study emphasizes the strength and range of HER-2 detection.HER-2 protein expression is divided into generalized type,partial type and focal type,and HER-2 gene is divided into cluster shape,big granular shape,point shape,and high polysomy,which can better provide quantitative reference index for the benefit in the process of targeted anti-tumor drug treatment.3.When detecting HER-2 gene of gastric cancer,the target of anti-tumor drug treatment Trastuzumab can be taken in amplification.Meanwhile,when detecting K-RAS gene,the target of anti-tumor drug treatment cetuximab can be chose,aiming at wild-type K-RAS gene.The joint detection of amplification of HER-2 gene and the mutation of K-RAS gene in gastric cancer can provide reference index for the benefit in the process of targeted anti-tumor drug treatment better.