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免疫抑制器官移植受者皮肤鳞状细胞发育异常和癌中人类乳头瘤病毒各型的E6/E7表达

E6/E7 expression of human papillomavirus types in cutaneous squamous cell dysplasia and carcinoma in immunosuppressed organ transplant recipients.

作者信息

Dang C, Koehler A, Forschner T, Sehr P, Michael K, Pawlita M, Stockfleth E, Nindl I

机构信息

Department of Dermatology, Charité, Skin Cancer Center Charité, University Hospital of Berlin, Charitéplatz 1, D-10117 Berlin, Germany.

出版信息

Br J Dermatol. 2006 Jul;155(1):129-36. doi: 10.1111/j.1365-2133.2006.07378.x.

DOI:10.1111/j.1365-2133.2006.07378.x
PMID:16792764
Abstract

BACKGROUND

DNA of cutaneous human papillomavirus (HPV) types is frequently found in nonmelanoma skin cancer, and their E6 and E7 proteins can have transforming properties.

OBJECTIVES

To assess the biological activity of HPV types found in tumour tissues we examined HPV E6/E7 RNA expression and the antibody response to E6, E7 and L1 proteins.

METHODS

Thirty-one snap-frozen biopsies from six immunosuppressed organ transplant recipients representing seven squamous cell carcinomas (SCCs), one basal cell carcinoma, four actinic keratoses (AKs), seven normal skin and 12 verrucae vulgaris (Vv) were analysed for 24 cutaneous HPV types by an L1 DNA polymerase chain reaction (PCR)-based method. The presence of E6/E7 transcripts of HPV 5, 8, 9, 15 and 20 was investigated by real-time reverse transcription-PCR. HPV DNA load was determined for HPV 8, 9 and 15 in 11 biopsies. Antibody response was measured by enzyme-linked immunosorbent assay using affinity-purified, bacterially expressed complete viral proteins fused to glutathione S-transferase as antigens.

RESULTS

HPV DNA was detected in 25 of 31 tissue samples, indicating eight single and 17 multiple HPV infections. E6/E7 transcripts of HPV 8, 9 and 15 were found in low copy numbers in one SCC and three AKs, but not in normal skin or Vv. All four patients examined showed antibodies to cutaneous HPV antigens, but the antibody response did not correlate with E6/E7 expression detected in the tumour.

CONCLUSIONS

Transcriptional activity of the E6/E7 oncogenes in AK and SCC suggests an active role of HPV in the lesion.

摘要

背景

皮肤型人乳头瘤病毒(HPV)的DNA在非黑素瘤皮肤癌中经常被发现,其E6和E7蛋白具有转化特性。

目的

为了评估在肿瘤组织中发现的HPV类型的生物学活性,我们检测了HPV E6/E7 RNA表达以及对E6、E7和L1蛋白的抗体反应。

方法

通过基于L1 DNA聚合酶链反应(PCR)的方法,对来自6名免疫抑制器官移植受者的31份速冻活检组织进行分析,这些组织代表7例鳞状细胞癌(SCC)、1例基底细胞癌、4例光化性角化病(AK)、7例正常皮肤和12例寻常疣(Vv),检测24种皮肤HPV类型。通过实时逆转录PCR研究HPV 5、8、9、15和20的E6/E7转录本的存在情况。测定11份活检组织中HPV 8、9和15的HPV DNA载量。使用与谷胱甘肽S-转移酶融合的亲和纯化的细菌表达的完整病毒蛋白作为抗原,通过酶联免疫吸附测定法测量抗体反应。

结果

在31份组织样本中的25份中检测到HPV DNA,表明有8例单一HPV感染和17例多重HPV感染。在1例SCC和3例AK中发现了低拷贝数的HPV 8、9和15的E6/E7转录本,但在正常皮肤或Vv中未发现。所有4名接受检查的患者均显示出针对皮肤HPV抗原的抗体,但抗体反应与肿瘤中检测到的E6/E7表达无关。

结论

AK和SCC中E6/E7癌基因的转录活性表明HPV在病变中起积极作用。

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