Detection of Merkel cell polyomavirus in cervical squamous cell carcinomas and adenocarcinomas from Japanese patients.
Detection of Merkel cell polyomavirus in cervical squamous cell carcinomas and adenocarcinomas from Japanese patients.
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DOI：
10.1186/1743-422x-9-154
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发表时间：
2012-08-09
期刊：
影响因子：
4.8
通讯作者：
Daibata M
中科院分区：
文献类型：
--
作者：
Imajoh M;Hashida Y;Nemoto Y;Oguri H;Maeda N;Furihata M;Fukaya T;Daibata M
默克尔细胞多瘤病毒（MCPyV）最初在默克尔细胞癌（MCC）（一种罕见的人类皮肤神经内分泌癌）中被鉴定。MCPyV存在于其他形式的恶性肿瘤，如皮肤鳞状细胞癌（SCC）的证据越来越多。宫颈癌成为我们寻找潜在MCPyV相关肿瘤的兴趣焦点，因为：（i）宫颈癌的主要组织学类型是SCC;（ii）宫颈是组织学上与MCC相似的神经内分泌癌的常见部位;（iii）MCPyV可能在性行为中传播，如人乳头瘤病毒（HPV）所示。在这项研究中，我们的目的是澄清可能存在的MCPyV在宫颈SCC从日本患者。还研究了宫颈腺癌（AC）。通过聚合酶链反应（PCR）和测序分析，对48例宫颈SCC和16例宫颈AC的福尔马林固定石蜡包埋组织样本进行了MCPyV基因组的检查。PCR检测结果显示9/48例宫颈SCC（19%）和4/16例宫颈AC（25%）为MCPyV DNA阳性。对MCPyV特异性PCR产物进行测序，以将其与参考序列进行比较。在MCPyV阳性的宫颈SCC和AC中，MCPyV大T（LT）测序区域的核苷酸序列是相同的。相反，在MCPyV病毒蛋白1（VP 1）测序区域，两个宫颈SCC和三个宫颈AC显示几个核苷酸取代，其中三个引起氨基酸取代。这些测序结果表明，在我们的病例中鉴定了VP 1的三种MCPyV变体。免疫组化结果显示，MCPyV阳性标本中的肿瘤细胞表达LT抗原。MCPyV阳性样本中的人HPV基因分型显示，SCC中感染的HPV为HPV 16、31和58型，AC中感染的HPV为HPV 16和18型。这项研究提供了第一个观察结果，即MCPyV共存于日本患者的HPV相关宫颈癌亚组中。这些病变中MCPyV的患病率接近皮肤SCC中观察到的患病率。进一步的全球流行病学调查是必要的，以确定可能的关联MCPyV与宫颈癌的发病机制。
Merkel cell polyomavirus (MCPyV) was identified originally in Merkel cell carcinoma (MCC), a rare form of human skin neuroendocrine carcinoma. Evidence of MCPyV existence in other forms of malignancy such as cutaneous squamous cell carcinomas (SCCs) is growing. Cervical cancers became the focus of our interest in searching for potentially MCPyV-related tumors because: (i) the major histological type of cervical cancer is the SCC; (ii) the uterine cervix is a common site of neuroendocrine carcinomas histologically similar to MCCs; and (iii) MCPyV might be transmitted during sexual interaction as demonstrated for human papillomavirus (HPV). In this study, we aimed to clarify the possible presence of MCPyV in cervical SCCs from Japanese patients. Cervical adenocarcinomas (ACs) were also studied. Formalin-fixed paraffin-embedded tissue samples from 48 cervical SCCs and 16 cervical ACs were examined for the presence of the MCPyV genome by polymerase chain reaction (PCR) and sequencing analyses. PCR analysis revealed that 9/48 cervical SCCs (19%) and 4/16 cervical ACs (25%) were positive for MCPyV DNA. MCPyV-specific PCR products were sequenced to compare them with reference sequences. The nucleotide sequences in the MCPyV large T (LT)-sequenced region were the same among MCPyV-positive cervical SCCs and AC. Conversely, in the MCPyV viral protein 1 (VP1)-sequenced region, two cervical SCCs and three cervical ACs showed several nucleotide substitutions, of which three caused amino acid substitutions. These sequencing results suggested that three MCPyV variants of the VP1 were identified in our cases. Immunohistochemistry showed that the LT antigen was expressed in tumor cells in MCPyV-positive samples. Genotyping of human HPV in the MCPyV-positive samples revealed that infected HPVs were HPV types 16, 31 and 58 for SCCs and HPV types 16 and 18 for ACs. This study provides the first observation that MCPyV coexists in a subset of HPV-associated cervical cancers from Japanese patients. The prevalence of MCPyV in these lesions was close to that observed in the cutaneous SCCs. Further worldwide epidemiological surveys are warranted to determine the possible association of MCPyV with pathogenesis of cervical cancers.