Clinical Significance Of HER2 Heterogeneity And Chromosome 17 Ploidy In Adenocarcinoma Of Stomach

Objective:Definite the relationship between HER2 heterogeneity and chromosome 17 ploidy and their clinical significance in gastric adenocarcinoma,by measuring the heterogeneity of HER2 and chromosome 17 ploidy.Methods:The protein overexpression and gene amplification of HER2 were determined by immunohistochemistry and fluorescence in situ hybridization in 153 patients with gastric adenocarcinoma,respectively,and the heteroplasmy cases and chromosome 17 ploidy were counted.SPSS21.0 statistical software was used for statistical analysis.Results:1.The numbers of patients with HER2 0,1+,2+ and 3+ were 92(60.1%),21(13.7%),19(12.4%),and 21(13.7%),respectively,when 153 cases with gastric adenocarcinoma were analysed.From FISH analysis,HER2 amplification was observed in 25 cases(16.3%).Most of them were low degree amplification.HER2 amplification was observed in 2(1.8%)out of 113 cases having an IHC score of 0/1+;HER2 amplification was observed in 5(26.3%)out of 19 cases having an IHC score of 2+,and in 18(85.7%)out of21 cases having an IHC score of 3+.The coincidence rates of IHC and FISH were 98.2%and 85.7% in the cases having an IHC score of 0~1+ and 3+(P<0.01),respectively.2.In 153 cases of gastric adenocarcinoma,the positive rate of HER2 was 18.3%(28/153),including 21 cases IHC 3+ and 7 cases IHC 0 ~ 2+/FISH+,which wassignificantly correlated with Lauren’s classification,depth of invasion and lymph node metastasis.The positive rate of HER2 in intestinal type gastric carcinoma was higher than that in mixed type and diffuse type(23.5% vs 10.7% vs 4.3%;P<0.05);The positive rate of HER2 in T1 and T2 stage was higher than that in T3~T4 stage(26.5% vs 36.4% vs11.3%;P<0.01);The positive rate of HER2 in patients with lymph node metastasis was higher than that in patients without lymph node metastasis(23.1% vs 6.7%;P<0.05).3.In 40 cases with gastric adenocarcinoma who have an IHC score of 2+ and 3+,phenotypic heterogeneity was observed in 31 cases(77.5%),including 18 cases of IHC 2+(94.7%)and 13 cases of IHC 3+(61.9%).In 25 cases of gastric adenocarcinoma with HER2 amplification,genetic heterogeneity was found in 12 cases(48.0%).The phenotypic heterogeneity of HER2 was correlated with Lauren’s classification and depth of invasion,the phenotype heterogeneity of HER2 in mixed type and diffuse type was higher than the intestinal type of gastric adenocarcinoma(100% vs 94.1% vs 60.0%;P<0.05),the phenotypic heterogeneity of HER2 in T1 and T2 stage was higher than in T3~T4 stage(92.3% vs 90.9% vs 56.3%;P<0.05).The genetic heterogeneity of HER2 was related to the depth of invasion,the genetic heterogeneity of HER2 in T1 and T2 stage was higher than that in T3~T4 stage(83.3 vs 62.5% vs 18.2%;P<0.05).4.In 153 cases of gastric adenocarcinoma,there are 114 cases(74.5%)with chromosome 17 diploid and 39 cases(25.5%)with aneuploidy,which including 8 cases(5.2%)with haploid and 31 cases(20.3%)with polyloid.The chromosome 17 polyloid rate in gastric adenocarcinoma with IHC 3+ of HER2 is higher than IHC 0~1+ and 2+(76.2%vs 8.8% vs 26.3%;P<0.01);The polyloid rate of chromosome 17 in gastric adenocarcinoma with HER2 gene amplification was higher than that in non-amplified gastric adenocarcinoma(60.0% vs 12.5%;P<0.01).There was no relationship between chromosome 17 aneuploid and HER2 phenotypic heterogeneity and genetic heterogeneity(P>0.05).5.Chromosome 17 aneuploidy is related to the location of gastric adenocarcinoma.the incidence of chromosome 17 polysomes in the proximal stomach is higher than in the stomach body and distal stomach(50.0% vs 11.4% vs 9.9%;P<0.05),there was nocorrelation with other clinicopathological features.Conclusion:The heterogeneity of HER2 was greater in gastric adenocarcinoma,phenotypic heterogeneity was significantly higher than genetic heterogeneity,and both of them are related to poor prognosis.Chromosome 17 aneuploidy may not be the cause of heterogeneity in gastric adenocarcinoma,however,it affects the determination of HER2 status in gastric cancer and is related to the poor prognosis of gastric adenocarcinoma.So in the course of the HER2 assay for gastric adenocarcinoma,these two factors should be considered in order to reduce the false positive rate and false negative rate.