Human papillomavirus infection in Egyptian esophageal carcinoma:: Correlation with p53, p21waf, mdm2, C-erbB2 and impact on survival
Human papillomavirus infection in Egyptian esophageal carcinoma:: Correlation with p53, p21waf, mdm2, C-erbB2 and impact on survival
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DOI：
10.1111/j.1440-1827.2005.01804.x
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发表时间：
2005-02-01
影响因子：
2.2
通讯作者：
Sherif, GM
中科院分区：
文献类型：
--
作者：
Bahnassy, AA;Zekri, ARN;Sherif, GM
探讨人乳头瘤病毒（HPV）与食管癌（EC）的病因学关系及其与p53、mdm 2、p21（waf）、c-erbB 2和总生存率（OS）的关系。采用聚合酶链反应和InnoLiPA检测50例食管癌的癌组织和正常组织中的HPV。采用单链构象多态性/测序法检测p53基因突变。免疫组化检测p53、mdm 2、p21（waf）和c-erbB 2的表达。在54%的肿瘤和24%的正常组织中检测到人乳头瘤病毒。p53、mdm 2和c-erbB 2在68%、70%和60%的肿瘤和14%、16%和10%的正常组织中检测到过表达，而p21（waf）在64%的肿瘤中明显缺失。20%的病例中检测到p53突变。外显子8和5显示出最高的突变率（各40%），其次是外显子6和7（各10%）。HPV与p53、mdm 2、c-erbB 2的过度表达有显著相关性。OS与p53的过度表达和p21（waf）的缺失显著相关。人乳头瘤病毒感染是常见的埃及EC。p53依赖性和p53非依赖性途径似乎都参与了HPV相关EC。mdm 2和c-erbB 2是p53非依赖性途径中HPV的可能靶点。然而，只有晚期和p53和p21（waf）的异常表达是独立的预后指标。
The etiological role of human papillomavirus (HPV) in esophageal carcinoma (EC) in relation to p53, mdm2, p21(waf), c-erbB2 and the overall survival (OS) rate was investigated. Tumor and normal tissues from 50 EC were evaluated by polymerase chain reaction and InnoLiPA for HPV. Single strand conformation polymorphism/sequencing were used to detect p53 gene mutations. Immunohistochemistry was performed to determine p53, mdm2, p21(waf)and c-erbB2 expression. Human papillomavirus was detected in 54% of tumors and in 24% of normal tissues. p53, mdm2 and c-erbB2 overexpression was detected in 68%, 70% and 60% of tumors and in 14%, 16% and 10% of normal samples, whereas loss of p21(waf) was evident in 64% of tumors. p53 mutations were detected in 20% of cases. Exon 8 and 5 showed the highest mutation rate (40% each), followed by exons 6 and 7 (10% each). There was a significant correlation between HPV and p53, mdm2, c-erbB2 overexpression. The OS was significantly associated with overexpression of p53 and loss of p21(waf). Human papillomavirus infection is frequent in Egyptian EC. Both p53-dependent and p53-independent pathways seem to be involved in HPV-associated EC. mdm2 and c-erbB2 are possible targets for HPV in the p53-independent pathway. However, only advanced stage and aberrant expression of p53 and p21(waf) are independent prognostic markers.