Clinical Factors Associated With Merkel Cell Polyomavirus Infection in Merkel Cell Carcinoma
Clinical Factors Associated With Merkel Cell Polyomavirus Infection in Merkel Cell Carcinoma
复制标题
DOI：
10.1093/jnci/djp139
复制
发表时间：
2009-07-01
影响因子：
10.3
通讯作者：
Joensuu, Heikki
中科院分区：
文献类型：
--
作者：
Sihto, Harri;Kukko, Heli;Joensuu, Heikki
默克尔细胞癌是一种罕见的皮肤恶性肿瘤。默克尔细胞多瘤病毒（MCPyV）DNA整合到肿瘤基因组中在这些癌症中是常见的。MCPyV感染的临床后果尚不清楚。我们分析了1979年至2004年芬兰207例确诊为默克尔细胞癌患者中114例福尔马林固定石蜡包埋的默克尔细胞癌组织样本，使用聚合酶链反应（PCR）、定量PCR、和DNA测序，并检查肿瘤MCPyV DNA状态与组织病理学因素和存活率之间的关联。存活受试者诊断为默克尔细胞癌后的中位随访时间为9.9年（范围= 4.9-21.9年）。91例（79.8%）癌组织中存在MCPyVDNA。与MCPyV DNA阴性癌症相比，MCPyV DNA阳性癌症更常位于肢体（40.7% vs 8.7%，P = 0.015），在诊断时有区域淋巴结转移的患者中较少发生（6.6% vs 21.7%，P = 0.043）。MCPyV DNA阳性肿瘤患者的总体生存率高于MCPyV DNA阴性肿瘤患者（5年生存率：分别为45.0%和13.0%; P <0.001，双侧对数秩检验）。MCPyV感染与默克尔细胞癌患者的临床结局相关。这些发现支持了病毒感染经常与默克尔细胞癌的发病机制相关的假设。
Merkel cell carcinoma is a rare malignancy of the skin. Integration of Merkel cell polyomavirus (MCPyV) DNA to the tumor genome is frequent in these cancers. The clinical consequences of MCPyV infection are unknown.We analyzed formalin-fixed paraffin-embedded Merkel cell carcinoma tissue samples from 114 of 207 patients diagnosed with Merkel cell carcinoma in Finland from 1979 to 2004 for the presence of MCPyV DNA with the use of polymerase chain reaction (PCR), quantitative PCR, and DNA sequencing and examined associations between tumor MCPyV DNA status and histopathologic factors and survival. The median follow-up time after Merkel cell carcinoma diagnosis for subjects who were alive was 9.9 years (range = 4.9-21.9 years). All P values are two-sided.MCPyV DNA was present in 91 carcinomas (79.8%). Compared with MCPyV DNA-negative cancers, MCPyV DNA-positive cancers were more often located in a limb (40.7% vs 8.7%, P = .015) and less frequent in patients who had regional nodal metastases at diagnosis (6.6% vs 21.7%, P = .043). Patients with MCPyV DNA-positive tumors had better overall survival than those with MCPyV DNA-negative tumors (5-year survival: 45.0% vs 13.0%, respectively; P < .001, two-sided log-rank test).MCPyV infection is associated with clinical outcomes in patients with Merkel cell carcinoma. These findings lend support to the hypothesis that viral infection is frequently associated with the pathogenesis of Merkel cell carcinoma.