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Toll样受体TLR4的下调与阴茎癌中HPV DNA整合相关。

Down-regulation of Toll-like Receptor TLR4 Is Associated with HPV DNA Integration in Penile Carcinoma.

作者信息

Damasdi Miklos, Kovacs Krisztina, Farkas Nelli, Jakab Ferenc, Kovacs Gyula

机构信息

Department of Urology, Medical School, University of Pecs, Pecs, Hungary.

Institute of Pathology, Medical School, University of Pecs, Pecs, Hungary.

出版信息

Anticancer Res. 2017 Oct;37(10):5515-5519. doi: 10.21873/anticanres.11982.

Abstract

BACKGROUND/AIM: Development of penile cancers is attributed to HPV-related carcinogenesis. Our aim was to analyze HPV positivity and TLR4, p16 and p53 expression.

MATERIALS AND METHODS

HPV presence was assessed with virus-specific TaqMan PCR and HPV Genotyping Test in 31 penile cancers. Immunohistochemistry was carried out on tissue microarray.

RESULTS

TLR4 expression was detected in 4 of the 16 HPV positive and 13 of the 15 HPV negative tumors. We found a significant inverse correlation between HPV positivity and TLR4 expression (p=0.0006). Ten of the 16 HPV-positive but none of the 15 HPV-negative tumors expressed p16INK4a. A significant correlation was seen between p53 expression and lack of HPV DNA (p=0.0191) as well as between TLR4 and p53 expression (p=0.0198) in penile cancers.

CONCLUSION

Our findings suggest a protective role of TLR4 expression against HPV DNA integration and the viral and non-viral carcinogenesis of penile cancer.

摘要

背景/目的:阴茎癌的发生归因于人乳头瘤病毒(HPV)相关的致癌作用。我们的目的是分析HPV阳性情况以及Toll样受体4(TLR4)、p16和p53的表达。

材料与方法

采用病毒特异性TaqMan聚合酶链反应(PCR)和HPV基因分型检测评估31例阴茎癌中的HPV存在情况。在组织芯片上进行免疫组织化学检测。

结果

在16例HPV阳性肿瘤中的4例以及15例HPV阴性肿瘤中的13例检测到TLR4表达。我们发现HPV阳性与TLR4表达之间存在显著的负相关(p = 0.0006)。16例HPV阳性肿瘤中有10例表达p16INK4a,而15例HPV阴性肿瘤中均无表达。在阴茎癌中,p53表达与HPV DNA缺失之间存在显著相关性(p = 0.0191),TLR4与p53表达之间也存在显著相关性(p = 0.0198)。

结论

我们的研究结果表明TLR4表达对HPV DNA整合以及阴茎癌的病毒和非病毒致癌作用具有保护作用。

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