Discordance of p53 status in matched primary tumours and metastases in head and neck squamous cell carcinoma patients

A. Kropveld , A.D.M. van Mansfeld , N. Nabben , G.J. Hordijk , P.J. Slootweg
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引用次数: 38

Abstract

To study the use of p53 as a diagnostic tool in head and neck squamous cell carcinoma (HNSCC), we analysed 15 primary tumours (PT) and matched lymph node metastases (LNM) for overexpression and mutations of p53. The primary goal was to study whether differentiation between primary and metastatic disease through their p53 status would be possible. Immunohistochemistry for p53 protein (antibody BP 53-12-1) was performed. Mutations of the p53 gene were detected by exonspecific amplification of DNA (exons 4–9), followed by exon analysis using denaturing gradient gel electrophoresis (DGGE). Mutant exons were sequenced. p53 overexpression was detected in seven (47%) of the PT and in seven (47%) of the LNM. 6 patients (40%) exhibited p53 protein overexpression in both PT and LNM. 2 patients had a different p53 protein expression in each sample. Mutations in the p53 gene were detected in 6 patients (40%) in the PT and in 7 patients (47%) in the LNM. In 2 patients (13%), the same mutation was found in the PT and in the LNM. 9 patients (60%) had a different mutation in each sample. We conclude that a poor correlation exists between p53 protein overexpression and p53 gene mutation in HNSCC. Also, a poor correlation for both detection techniques exists, when PT and LNM are compared. The p53 status may seem to differ between PT and LNM because of polyclonality in the PT. More sensitive detection techniques could be promising.

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头颈部鳞状细胞癌患者匹配原发肿瘤和转移瘤中p53状态的不一致
为了研究p53作为头颈部鳞状细胞癌(HNSCC)的诊断工具,我们分析了15例原发性肿瘤(PT)和匹配的淋巴结转移(LNM)中p53的过表达和突变。主要目的是研究是否可以通过p53状态来区分原发性和转移性疾病。对p53蛋白(抗体BP 53-12-1)进行免疫组化检测。通过DNA外显子扩增(4-9外显子)检测p53基因的突变,然后使用变性梯度凝胶电泳(DGGE)进行外显子分析。对突变外显子进行测序。在7例(47%)PT和7例(47%)LNM中检测到p53过表达。6例患者(40%)在PT和LNM均表现出p53蛋白过表达。2例患者在每个样本中p53蛋白表达不同。6例(40%)PT患者和7例(47%)LNM患者检测到p53基因突变。在2例患者(13%)中,在PT和LNM中发现了相同的突变。9例患者(60%)在每个样本中有不同的突变。我们得出结论,p53蛋白过表达与HNSCC中p53基因突变之间存在较低的相关性。此外,当PT和LNM进行比较时,两种检测技术的相关性都很差。由于PT的多克隆性,p53的状态似乎在PT和LNM之间有所不同。更敏感的检测技术可能是有希望的。
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