Hypermethylation of the thrombospondin-1 gene is associated with poor prognosis in penile squamous cell carcinoma
Hypermethylation of the thrombospondin-1 gene is associated with poor prognosis in penile squamous cell carcinoma
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DOI：
10.1111/j.1464-410x.2008.07603.x
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发表时间：
2008-09-01
影响因子：
4.5
通讯作者：
Puras, Ana
中科院分区：
文献类型：
--
作者：
Guerrero, David;Guarch, Rosa;Puras, Ana
为评估人乳头瘤病毒（HPV）感染的存在，检测了人宫颈癌组织中血小板反应蛋白-1（TSP-1）、RAS相关结构域家族1A（RAS association domain family 1A）基因启动子区甲基化状态。（RASSF 1-A）和p16基因，以及TSP-1、CD 31、p16和p53蛋白在诊断为阴茎癌的患者中的表达，以及这些变量与临床和病理特征之间的可能关联。应用反向线性杂交、甲基化特异性聚合酶链反应和免疫组化方法分别检测了24例阴茎鳞状细胞癌的基因启动子甲基化和蛋白表达情况，其中11例（46%）检测到HPV感染，TSP-1、RASSF 1-A和p16基因甲基化率分别为46%、42%和38%。TSP-1高甲基化与不良的组织学分级（3级; P = 0.033）、血管浸润（P = 0.023）、TSP-1蛋白弱表达（P = 0.041）和较短的总生存期（P = 0.04）相关。TSP-1表达与微血管密度无关。然而，RASSF 1-A高甲基化在T1肿瘤中更常见（P = 0.01），而p16高甲基化与除p16表达缺失外的任何测试变量均不相关（P = 0.022）。总之，TSP-1和RASSF 1-A基因的表观遗传失活与病理变量相关，似乎在阴茎癌中具有预后意义。
To evaluate the presence of human papillomavirus (HPV) infection, the methylation status in the promoter region of thrombospondin-1 (TSP-1), RAS association domain family 1A (RASSF1-A) and p16 genes, and the expression of TSP-1, CD31, p16 and p53 proteins in patients diagnosed with penile cancer, and the possible associations between these variables and clinical and pathological features.HPV types, gene promoter hypermethylation and protein expression were analysed by reverse line blot, methylation-specific polymerase chain reaction, and immunohistochemistry, respectively, in 24 penile squamous cell carcinomas.HPV infection was detected in 11 of 24 cases (46%), and TSP-1, RASSF1-A and p16 genes were hypermethylated in 46%, 42% and 38% of the tumours, respectively. TSP-1 hypermethylation was associated with unfavourable histological grade (grade 3; P = 0.033), vascular invasion (P = 0.023), weak expression of TSP-1 protein (P = 0.041), and shorter overall survival (P = 0.04). TSP-1 expression was not associated with microvessel density. However, RASSF1-A hypermethylation was more frequent in T1 tumours (P = 0.01), and p16 hypermethylation was not associated with any of the tested variables except for absence of p16 expression (P = 0.022).In summary, the epigenetic inactivation of TSP-1 and RASSF1-A genes is associated with pathological variables and seems to be of prognostic significance in penile cancer.