PDF(Pubmed)
Abstract：
The aim of this study was to determine whether the expression of CHK2 and p53 in tumor tissue in carriers of germline CHEK2 mutations can serve as a prognostic marker for PTC, and whether CHEK2 and TP53 copy numbers correlates with the course of PTC disease. This study included 156 PTC patients previously tested for the presence of CHEK2. Clinicopathological features, treatment response, disease outcome, and germline mutation status of the CHEK2 gene were assessed with respect to CHK2 and p53 expression, and CHEK2 and TP53 gene copy statuses. In patients with and without a germline mutation in CHEK2 and with higher CHK2 expression, the chances of an excellent treatment response and no evidence of disease were lower than in patients without or with lower CHK2 expression. TP53 deletion was associated with angioinvasion. In patients with a truncating mutation, the chance of a CHEK2 deletion was higher than in patients with WT CHEK2 alone or those with WT CHEK2 and with the missense I157T mutation. Higher CHK2 expression was associated with poorer treatment responses and disease outcomes. Higher CHK2 expression and positive p53 together with a TP53 deletion could be a prognostic marker of unfavorable disease outcomes in patients with germline truncating mutations in CHEK2.
摘要：
这项研究的目的是确定CHK2和p53在种系CHEK2突变携带者的肿瘤组织中的表达是否可以作为PTC的预后标志物。CHEK2和TP53拷贝数是否与PTC病程相关。这项研究包括156名之前测试CHEK2存在的PTC患者。临床病理特征,治疗反应,疾病结果,CHEK2基因的种系突变状态与CHK2和p53表达有关，和CHEK2和TP53基因拷贝状态。在CHEK2有和没有种系突变和CHK2表达较高的患者中，与无CHK2表达或CHK2表达较低的患者相比,获得优异的治疗应答和无疾病证据的机会较低.TP53缺失与血管浸润有关。在具有截断突变的患者中，CHEK2缺失的机率高于单纯使用WTCHEK2的患者或患有WTCHEK2且有错义I157T突变的患者.较高的CHK2表达与较差的治疗反应和疾病结局相关。较高的CHK2表达和阳性p53以及TP53缺失可能是CHEK2种系截断突变患者不良疾病结局的预后标志物。
