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Clinical Epidemidogical Study Of HER-2/neu Expression In1363Cases Of Gastric Cancer

Posted on:2014-02-27Degree:MasterType:Thesis
Country:ChinaCandidate:K Y WangFull Text:PDF
GTID:2234330395997481Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Gastric cancer is the common malignant tumor in the world. Its incidenceoccupies the forth place,and the mortality is secondary. The spread and the transfer ofthe gastric cancer are the important reason that leaded to the deaths of patients.Numerous studies have confirmed that, because of different reasons, the most patientswith gastric cancer have been diagnosed when they have been in the advancedphase—transfers what have already happened or the locally advanced gastric cancerwhich can’t accept the surgery. Although taking the alleviative treatment, thefive-year survival rate of the patients with locally advanced gastric cancer ormetastatic gastric cancer is still between5%--20%, and the median overall survival islack of one year, ToGA research which was reported at ASCO meeting in2009, firstlyconformed that the combination chemotherapy of the trastuzumab could improve thesurvival of the Positive patients with advanced HER-2/neu gastric cancer, and couldmake the overall survival of the patients be over one year, until13.8mouths. Andnormally the mean survival time of the patients with locally advanced gastric cancer isonly between10to12months; At the same time, the response rate(RR) is increasedfrom34.5%to47.3, and the RR of the normal Gastric cancer chemotherapy is about30%. It turns a new leaf about the Gastric cancer targeted therapy.HER-2/neu is proto-oncogene, locating in Human chromosome17q21. Its encoding is made up of1225transmembrane protein p185with Molecular weight of185kd, and belongs to the EGFR family with HER-1(EGFR)、HER-3、HER-4. HER-2/neu mainly expressed in embryonic development, being involvedin the regulation of cell growth, proliferation and differentiation; It can be checked only a little from the normal tissue, and its Abnormal amplification or the over-expression of p185is closely related with the happening and development of different cancers. The2main conduction paths of HER-2/neu participates in, can activate mitogen activated protein kinase, MAPK and prosphatidylinos itol3kinase-protein kinase/Akt,PI3K/Akt. The former one participates Cell mitosis; and the latter one mainly effect the Survival and apoptosis of the cells.HER-2/neu is one of the prognosis factors on breast cancer. The Clinicalcharacteristics of the positive (Expression or amplification) HER-2/neu breast cancerhave the special expression with biological behavior, and its treatment mode is quitedifferent from other kinds of breast cancer. At the same time, more and more scholarspay attention on the correlation research of HER-2/neu and gastric cancer, and makesome progress. One of the most concerns was ToGA clinical research which wasbrought out in the ASCO meeting in2009. It is the first randomized, prospective,multicentric Ⅲ phase clinical trials which study atTrastuzumab can’t be cured bysurgery and recurrence/metastasis HER-2/neu positive gastric cancer. It is also thelargest clinical study until now. In this research, after checking3655volunteer, theheterogeneity rate of HER-2/neu expressing in gastric cancer tissue is higher; thebasolateral membrane of gland cell reaction increases, leading to the incompletemembrane reaction. According to these differences, the expert group suggests a newHER-2/neu rating and testing standards in the ToGA test; and uses the IHC and FISHdetection at the same time. The final result is810(2.1%) patients getting positive(IHC2+/FISH+或IHC3+). The positive rate is similar in Asian and European peopl(e23.5%:23.6%), and has some differences with the different Tumor site. The HER-2/neupositive rate of Gastro esophageal junction cancer is higher than the positive rate ofgastric cancer(33.2%:20.9%;p=0.001),and the HER-2/neu positive rate of Intestinaltype of gastric cancer is higher than Diffuse type/hybrid gastric cancer(32.2%:6.1%/20.4%;p=0.001). But after summarizing literature, the expression of HER-2/neu ingastric cancer are quite different, the protein expression rate is6%to34%. It willconnect with the higher gastric cancer tumor heterogeneity, the study’s sample sizedifferences, different testing method and criteria, and the racial difference. And in theregion, the case of standardized analysis of HER-2/neu expressing in gastric cancerthat combined with the clinical pathological parameters, has not been reported.Aim: Test the expression of the Specimen HER-2/neu of gastric cancer (2006--2012), and discussing the relevance of HER-2/neu and gastric cancer’s development andprogression, pathological patterns and stages.Method: Collecting the1363wax blocks after gastric cancer surgery during2006to2012, using ICH to test the expression of HER-2/neu protein, test the HER-2/neu genemagnification of the immunohistochemical suspicious positive specimens by FISH,thenanalysis the relationship of the testing results and the clinical pathologicalparameters of the patients.Result:1.By using IHC and FISH to check the expression of HER-2/neu, the positiverate is14.53(198/1363); IHC3+is142, expression percentage is10.42%; HER-2/neuIHC(2+) is87, expression percentage is6.38%; IHC0~1+is1134(83.20%). To dothe FISH detection,56has in HER-2/neu gene amplification (64.37%).2.The positiverate of Well-differentiated adenocarcinoma(32/149)is21.48%; The positive rate ofmoderately differentiated adenocarcinoma (96/450) is21.33%; The positive rate ofpoorly differentiated adenocarcinoma(70/764) is9.16%. Comparison of two, thepositive rate of the Well-differentiated and moderately differentiated adenocarcinomais higher than tha positive way of poorly differentiated adenocarcinoma, thedifference is statistically significant (p<0.0001). But it has no sense between thefront two situations.3.The positive rate of GEJC is27.09%;The positive rate of thebody of the gastric cancer is7.64%;The positive rate of the gastric antrum is13.30%;The positive rate of the stomach angle is7.02%;The positive rate of the totalgastric cancer is0.00%.The difference is statistically significant(p<0.0001).4.Thepositive rate of intestinal is19.59%;The positive rate of the body of diffuse is8.92%;The positive rate of hybrid is12.50%.The difference is statistically significant(p<0.0001).5.The positive rate of male is15.46%;The positive rate of female is11.99%.The difference isn’t statistically significant (p=0.107).6.The positive rate ofthe patients over60years old is14.78%;The positive rate of less than60is14.26%.The difference isn’t statistically significant(p=0.786).7.The positive rate ofthe Han nationality is14.44%;The positive rate of the Manchu is19.05%;The positiverate of the Hui nationality is0.00%;The positive rate of the Mongol nationality is 11.76%;The positive rate of the Korean patients is33.33%.The difference isn’tstatistically significant (p=0.613).8.The positive rate of the tumor≥5cm is16.08%;The positive rate of the tumor<5cm is13.10%.The difference isn’tstatistically significant(p=0.119).9.The positive rate of the canalicular adenoma is14.95%;The positive rate of the mucinous adenocarcinoma is11.96%;The positiverate of the papillary adenocarcinoma is28.57%;The positive rate of the signet-ringcell carcinoma is6.38%.The difference isn’t statistically significant(p=0.232).10.The positive rate of T1is15.95%;The positive rate of T2is14.45%;The positiverate of T3is18.18%;The positive rate of T4is14.00%.The difference isn’tstatisticallysignificant(p=0.747).11.The positive rate of N1is16.58%;The positiverate of N2is12.02%;The positive rate of N3is13.86%;The positive rate of N4is16.15%.The difference isn’t statistically significant (p=0.400).12.The positive rateof M0is14.38%;The positive rate of M1is15.91%.The difference isn’t statisticallysignificant(p=0.635).13.The positive rate of stage I is14.72%;The positive rate ofstage II is13.03%;The positive rate of stage III is14.76%;The positive rate of stageIV is15.91%.The difference isn’t statistically significant(p=0.881).14.The positiverate of the patients with liver metastasis is19.05%;The positive rate of the patients notwith liver metastasis is14.23%.The difference isn’t statistically significant(p=0.169).15.The positive rate of storage of specimens of1-3years is17.88%;Thepositive rate of storage of specimens from4to7years is10.99%.The difference isstatistically significant(p<0.0001).Conclusion:1.1363after resection of gastric cancer specimens from2006to2012,the positive rate of HER-2/neu is14.53%.2. Protein overexpression and geneamplification of HER-2/neu have some relationships with the integration of a stomachesophagus cancer, Intestinal type of gastric cancer and High moderately differentiatedgastric cancer.3. The standardization of HER-2/neu interpretation testing proceduresand results in the gastric cancer are the premises of the benefit from trastuzumabtreatment for the patients.4. Through this study, the clinical epidemiological studies of HER-2/neu expressing in1363cases of gastric cancer provide a reference for cancer targeted therapy.
Keywords/Search Tags:gastric cancer, HER-2/neu, immunohistochemical, fluorescence in situ hybridization, clinicopathologic feature
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