Higher Expression of Activation-induced Cytidine Deaminase Is Significantly Associated with Merkel Cell Polyomavirus-negative Merkel Cell Carcinomas
Higher Expression of Activation-induced Cytidine Deaminase Is Significantly Associated with Merkel Cell Polyomavirus-negative Merkel Cell Carcinomas
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DOI：
10.33160/yam.2017.09.002
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发表时间：
2017-09-01
影响因子：
1
通讯作者：
Hayashi, Kazuhiko
中科院分区：
文献类型：
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作者：
Matsushita, Michiko;Iwasaki, Takeshi;Hayashi, Kazuhiko
研究背景Merkel细胞癌(MCC)是临床侵袭性神经内分泌皮肤癌，分为Merkel细胞多瘤病毒(MCPyV)阳性和阴性肿瘤，具有不同的临床病理特征，可能通过不同的致癌机制发生。在幽门螺杆菌相关性胃癌、成人T细胞白血病/淋巴瘤(HTLV-1)、肝癌和Burkitt淋巴瘤(EBV)中，激活诱导胞苷脱氨酶(AID)作为一种基因组调节因子在病原体相关的胃癌、成人T细胞白血病/淋巴瘤(HTLV-1)、肝癌和Burkitt淋巴瘤(EBV)中异常表达。方法采用免疫组织化学方法检测24例MCPyV阳性和17例MCPyV阴性MCC中AID和AID调节因子的表达。结果MCPyV阴性MCC中AID表达显著高于MCPyV阳性MCC(P=0.026)。尽管MCPyV阳性MCC中NF-kappa B p65(磷酸化S536)的表达显著高于MCPyV阴性MCC(P=0.034)。PAX5和c-Myb在各亚组间的表达差异无统计学意义。结论虽然病原体通过上调核因子-kappaB诱导的AID表达可能与MCPyV阳性MCC的发生有关，但MCPyV阴性MCC的AID异常表达显著高于MCPyV阳性MCC，这与MCPyV阴性MCC突变负荷极高的事实相一致。
Background Merkel cell carcinomas (MCCs), clinically aggressive neuroendocrine skin cancers, are divided into Merkel cell polyomavirus (MCPyV)-positive and -negative tumors, which show different clinicopathological features and may develop through different mechanisms of carcinogenesis. Aberrant expression of activation-induced cytidine deaminase (AID) as a genomic modulator was demonstrated through pathogen-related NF-kappa B signal in Helicobacter pylori-associated gastric cancer, adult T cell leukemia/lymphoma (HTLV-1), hepatoma (HCV), and Burkitt lymphoma (EBV).Methods To elucidate the relation of aberrant AID expression in MCPyV-positive and -negative MCCs, we evaluated immunohistochemical expressions of AID and AID-regulating factors between 24 MCPyV-positive and 17 MCPyV-negative MCCs.Results AID expression was significantly higher in MCPyV-negative MCCs than MCPyV-positive ones (P = 0.026), although expression of NF-kappa B p65 (phospho S536) (AID-enhancer) was significantly higher in MCPyV-positive MCCs than MCPyV-negative ones (P = 0.034). Expressions of PAX5 and c-Myb were not significantly different between these subgroups. Expressions of AID and AID-regulating factors were not correlated to prognosis of MCC patients.Conclusion Our findings suggest that although pathogen-induced AID expression through upregulation of NF-kappa B may be relevant to carcinogenesis of MCPyV-positive MCCs, the significantly higher aberrant AID expression in MCPyV-negative MCCs is consistent with the fact that MCPyV-negative MCCs have an extremely higher mutation burden than MCPyV-positive ones.