JC virus infection in colorectal neoplasia that develops after liver transplantation.
JC virus infection in colorectal neoplasia that develops after liver transplantation.
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DOI：
10.1158/1078-0432.ccr-08-0961
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发表时间：
2008-10-15
期刊：
影响因子：
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通讯作者：
Boland CR
中科院分区：
文献类型：
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作者：
Selgrad M;Koornstra JJ;Fini L;Blom M;Huang R;Devol EB;Boersma-van Ek W;Dijkstra G;Verdonk RC;de Jong S;Goel A;Williams SL;Meyer RL;Haagsma EB;Ricciardiello L;Boland CR
肝移植受体（LTRs）患结肠直肠癌的风险增加。造成这种情况的机制尚不清楚。JCV编码TAg，并与结直肠癌的发生有关。我们假设在LTRs中使用免疫抑制促进了JCV的激活，并导致了瘤变风险的增加。在LTRs正常结肠上皮（n = 15）和腺瘤性息肉（n = 26）中检测JCV TAg DNA和蛋白表达，并与对照患者（正常结肠，n = 21；腺瘤，n = 40）的组织样本进行比较。M30和Ki-67免疫反应分别检测细胞凋亡和细胞增殖。15例LTRs正常结肠黏膜中有10例（67%）检测到JCV TAg DNA， 21例对照正常粘膜中有5例（24%）检测到JCV TAg DNA （P = 0.025）。26例LTRs腺瘤中有16例（62%）检测到JCV TAg DNA， 40例对照腺瘤中有20例（50%）检测到JCV TAg DNA。来自ltr的26个腺瘤中有13个（50%）表达JCV TAg蛋白，而来自对照组的40个腺瘤中有2个（5%）表达JCV TAg蛋白（P < 0.001）。ltr腺瘤的平均增殖活性高于对照组（60.3±3.2%比42.7±2.8%,P < 0.001），而ltr腺瘤的平均凋亡指数低于对照组（0.29±0.08%比0.39±0.06%,P = 0.05）。JCV在ltr结肠粘膜和腺瘤中的存在，以及免疫抑制剂的使用，表明JCV可能经历了再激活，随后的TAg蛋白表达可能解释了ltr结直肠瘤变风险增加的原因。
Liver transplant recepients (LTRs) have an increased risk of colorectal neoplasia. The mechanism responsible for this is unknown. JCV encodes for TAg and has been implicated in colorectal carcinogenesis. We hypothesized that the use of immunosuppression in LTRs facilitates activation of JCV and is responsible for the increased risk of neoplasia. JCV TAg DNA and protein expression were determined in normal colonic epithelium (n = 15) and adenomatous polyps (n = 26) from LTRs and compared with tissue samples from control patients (normal colon, n = 21; adenomas, n = 40). Apoptosis and proliferation were determined by M30 and Ki-67 immunoreactivity, respectively. JCV TAg DNA was found in 10 of 15 (67%) of normal colonic mucosa from LTRs compared with 5 of 21 (24%) of control normal mucosa (P = 0.025). JCV TAg DNA was detected in 16 of 26 (62%) of the adenomas from LTRs and in 20 of 40 (50%) of control adenomas. JCV TAg protein was expressed in 13 of 26 (50%) adenomas from LTRs versus 2 of 40 (5%) of adenomas from controls (P < 0.001). In adenomas from LTRs, the mean proliferative activity was higher compared with controls (60.3 ± 3.2% versus 42.7 ± 2.8%, P < 0.001), whereas mean apoptotic indices were lower in LTRs (0.29 ± 0.08% versus 0.39 ± 0.06%, P = 0.05). The presence of JCV in the colorectal mucosa and adenomas from LTRs, in concert with the use of immunosuppressive agents, suggests that JCV may undergo reactivation, and the subsequent TAg protein expression might explain the increased risk of colorectal neoplasia in LTRs.