p53 mutations in deep tissues are more strongly associated with recurrence than mutation-positive mucosal margins
p53 mutations in deep tissues are more strongly associated with recurrence than mutation-positive mucosal margins
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DOI：
10.1158/1078-0432.ccr-07-1369
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发表时间：
2007-10-15
影响因子：
11.5
通讯作者：
Partridge, Max
中科院分区：
文献类型：
--
作者：
Huang, Xiaohong;Pateromichelakis, Stelios;Partridge, Max
目的：应用超敏诊断法发现，头颈部鳞状细胞癌切除后，组织学正常组织中有少量p53突变阳性细胞可能提示肿瘤残留。迄今为止，该领域的大多数研究都集中在对切除的粘膜组织进行分析，并强调了该领域中分子变化对复发风险的重要性。实验设计：在目前的研究中，我们分析了粘膜和深部手术边缘（称为“分子边缘”）的正常组织，以确定每种肿瘤中存在的标志性p53突变。结果：这些癌的p53突变状态与临床或组织病理学变量无关，但这些突变为边缘状态的超灵敏分析提供了一个很好的目标。我们发现16例组织学上无肿瘤（包括9例无发育不良）但p53突变阳性分子边缘的患者中有11例（68%）复发。与清晰边缘组相比，p53突变阳性边缘组局部复发的概率显著更高（P = 0.048），与p53突变阳性的深层分子边缘比突变阳性的粘膜分子边缘或两者均阳性的深层分子边缘的相关性更强（P = 0.009）。结论：这表明，尽管持续的粘膜野区可能导致复发，但深层组织的克隆性p53突变是治疗失败的重要原因，在未来的前瞻性系列中，应分析这两个部位的分子边界。
Purpose: Application of ultrasensitive diagnostics has shown that small numbers of p53 mutation-positive cells may signify the presence of residual tumor in histologically normal tissues after resection of squamous cell carcinomas arising in the head and neck area. To date, most studies in this area have focused on analysis of tissues at the mucosal aspect of the resection and highlighted the importance of molecular changes in the field with respect to the risk of recurrence.Experimental Design: In the present investigation, we analyzed normal tissues from mucosal and deep surgical margins, referred to as "molecular margins," for the presence of the signature p53 mutation identified for each tumor.Results: The p53 mutation status of these carcinomas did not correlate with clinical or histopathologic variables, but these mutations provided an excellent target for ultrasensitive analysis of margin status. We found that 11 of 16 (68%) of cases with histologically tumor-free (including 9 without dysplasia), but with p53 mutation-positive molecular margins, developed recurrence. The probability of developing local recurrence was significantly higher for the group with p53 mutation-positive margins when compared with the group with clear margins (P = 0.048) and more strongly associated with p53 mutation- positive deep molecular margins than mutation-positive mucosal molecular margins or positivity at both sites (P = 0.009).Conclusions: This shows that although persistent mucosal fields may contribute to recurrence, clonal p53 mutations in deep tissues are an important cause of treatment failure, and molecular margins from both sites should be analyzed in future prospective series.