Detection And Analysis On Apoptosis And Abnormal Expression Of C-myc And Ki-67 In Epstein-Barr Virus-associated Gastric Carcinoma

Objective In order to invegative the role of EBV infenction in gastric carcinoma, we compared the rate of apoptosis and the expression of c-myc and Ki-67 in EBV-associated gastric carcinoma(EBVaGC) and EBV-negative gastric carcinomas. Methods The apoptotic cells was tested by terminal deoxynucleotidyl transferase(TdT)-mediated dUTP-biotin nick end labelling(TUNEL),and the expression of c-myc and Ki-67 protein were tested by immunohistochemistry in 13 EBVaGCs and 45 EBVnGCs with matched clinicopathological data.The expression of EBV coded genes were tested by RT-PCR and Southern blotting.Results①The transcripts of EBNA1 was detected in all of 13 EBVaGCs,but no EBNA2 and LMP1 transcripts were detected in 13 cases.Of the 13 EBV-positive samples,6 exhibited BARF1 transcript and 2 exhibited BHRF1 transcript.②Ki-67 index of EBVaGC and EBVnGC were 28.254±6.284 and 37.864±14.523,respectively. The KI had a significant difference between EBVaGC and EBVnGC tissues(t' =3.458,P＜0.01).③The Ki-67 index was 35.716±15.091 in gastric carcinomas, 31.817±10.332 in paracarcinomas with precancerous lesion and 12.441±10.912 paracarcinomas without precancerous lesion.The Ki-67 index in gastric carcinomas and paracarcinomas with precancerous lesion was higher than in paracarcinomas without precancerous lesion and there was significant difference between them (P＜0.01).④The expression of c-myc protein was detectded in 33 of 58(55.39%) gastric carcinomas and in 21 of 58(36.21%) adjacent tissues.There was significant difference between the two groups(x~2=5.042,P＜0.05).The expression of c-myc protein was detectded in 8 of 13(61.54%) EBVaGCs and in 25 of 45 (55.56%)EBVnGCs.The difference between the two groups was not significant (x~2=0.147,P＞0.05).⑤AI of EBVaGCs,EBVnGCs and the corresponding adjacent tissues of EBVaGCs were 0.969±0.413,2.033±0.600 and 3.254±0.459 respectively. AI of EBVaGC was significantly lower than that of EBVnGC(t=5.979,P＜0.05) and orresponding adjacent tissues of EBVaGC(t=13.343,P＜0.01).AI was significantly lower in c-myc-postive tumors than c-myc -negative tumors(t=5.206,P＜0.01).Conclusions①The c-myc expression did not correlate with the presence of EBV in EBVaGC.EBV might inhibit cell apoptosis,however,the mechanism by which EBV inhibit cell apoptosis did not induce Ki-67 and c-myc expression.②The significant low rate of apoptosis was recognized in EBV-positive gastric carcinomas,suggesting that EBV infection may play a role in the development and progression of gastric carcinoma③EBNA2 and LMP1 did not correlate with the cell proliferation and c-myc expression in the EBVaGC.Early genes BARF1 and BHRF1 might play an important role in the development and progression of EBVaGC by the mechanisms of inducing c-myc protein expression and inhibiting cell apoptosis.