Merkel cell carcinoma subgroups by Merkel cell polyomavirus DNA relative abundance and oncogene expression.

Merkel cell carcinoma subgroups by Merkel cell polyomavirus DNA relative abundance and oncogene expression.
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DOI:
10.1002/ijc.24676
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发表时间:
2010-05-01
影响因子:
6.4
通讯作者:
Ayers, Leona W.
Ayers, Leona W.
中科院分区:
医学1区
文献类型:
--
作者:
Bhatia, Kishor;Goedert, James J.;Modali, Rama;Preiss, Liliana;Ayers, Leona W.

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默克尔细胞多瘤病毒(MCPyV)是近年来在皮肤神经内分泌细胞的一种临床和病理异质性恶性肿瘤默克尔细胞癌(MCC)中发现的。为了研究这种异质性,我们开发了一种组织芯片(TMA)来表征候选肿瘤细胞蛋白的免疫组化染色和定量PCR检测MCPyV和测量病毒载量。在23例原发性MCC肿瘤中的19例(74%)中检测到MCPyV,但其中8例每300个细胞中的病毒拷贝数小于1。免疫组化结果显示,视网膜母细胞瘤病毒丰度为0.06- 1.2拷贝/细胞与视网膜母细胞瘤基因产物(pRb)和末端脱氧核糖核苷酸转移酶(TdT)的存在直接相关(P≤0.003)。较高病毒丰度的肿瘤倾向于与较低的p53表达、较年轻的诊断年龄和较长的生存期相关(P≤0.08)。这些数据表明MCC可能通过不同的致癌途径产生,包括不依赖于pRb和MCPyV的途径。
Merkel cell polyomavirus (MCPyV) was recently discovered in Merkel cell carcinoma (MCC), a clinically and pathologically heterogeneous malignancy of dermal neuroendocrine cells. To investigate this heterogeneity, we developed a tissue microarray (TMA) to characterize immunohistochemical staining of candidate tumor cell proteins and a quantitative PCR assay to detect MCPyV and measure viral loads. MCPyV was detected in 19 of 23 (74%) primary MCC tumors, but 8 of these had less than 1 viral copy per 300 cells. Viral abundance of 0.06–1.2viral copies/cell was directly related to presence of retinoblastoma gene product (pRb) and terminal deoxyribonucleotidyl transferase (TdT) by immunohistochemical staining (P≤0.003). Higher viral abundance tumors tended to be associated with less p53 expression, younger age at diagnosis, and longer survival (P≤0.08). These data suggest that MCC may arise through different oncogenic pathways, including ones independent of pRb and MCPyV.
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