Mutated p53 as a molecular marker for the diagnosis of head and neck cancer
Mutated p53 as a molecular marker for the diagnosis of head and neck cancer
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DOI：
10.1002/path.1242
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发表时间：
2002-12-01
影响因子：
7.3
通讯作者：
Brakenhoff, RH
中科院分区：
文献类型：
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作者：
van Houten, VMM;Tabor, MP;Brakenhoff, RH
总共，10-30%的头颈鳞状细胞癌（HNSCC）患者尽管看似充分切除了肿瘤，但仍出现局部复发。这可能是由于微小残留癌（MRC：手术边缘残留少量肿瘤细胞，常规组织病理学无法检测到）造成的。在最近的研究中。p53突变被认为是癌细胞的选择性和敏感DNA标记。使用p53突变存在两个潜在问题 突变的 p53 DNA 作为标记。首先。 p53 突变发生在进展早期，因此可能会检测到除肿瘤细胞外未切除的前体病变。其次，DNA是一种非常稳定的生物分子，可能会导致假阳性结果。本研究对这两个潜在问题进行了评估。纳入了 50 名接受根治性肿瘤切除的患者，其中 30 名原发肿瘤显示 p53 突变。组织病理学上 通过分子诊断（斑块测定）和随后的（免疫）组织病理学对无肿瘤手术切缘的 p53 突变进行定量分析。在 19130 名患者的手术切缘中检测到 p53 突变 DNA。免疫组织化学证实 2/19 突变 p53 阳性病例中存在小肿瘤灶。在 7/19 的情况下， 在未切除的发育不良粘膜前体病变中发现了肿瘤特异性 p53 突变。此外，在许多情况下，检测到小的 p53 免疫染色斑块，但发现的突变从未与肿瘤相关。通过筛选对侧脱落细胞和 RNA 噬菌斑测定，结果表明检测突变 p53 DNA 很容易出现假阳性结果。总之，使用 以 p53 突变作为标记，在手术切缘内检测到 MRC 和未切除的突变 p53 阳性粘膜前体病变。使用 p53 突变对手术切缘进行分子评估可以选择肿瘤复发高风险的 HNSCC 患者，但目前肿瘤 RNA 似乎是比肿瘤 DNA 更具体的分析生物分子。 (C) 版权所有 2002 约翰 威利儿子有限公司
In total, 10-30% of patients with head and neck squamous cell carcinoma (HNSCC develop local recurrences despite seemingly adequate tumour resection. This may result from minimal residual cancer (MRC: small numbers of tumour cells left behind in the surgical margins, undetectable by routine histopathology. In recent studies. p53 mutations have been considered as selective and sensitive DNA markers of cancer cells. There are two potential problems in using mutated-p53 DNA as a marker. Firstly. p53 mutations occur early in progression and might therefore detect unresected precursor lesions besides tumour cells. Secondly, DNA is a very stable biomolecule that might lead to false-positive results. These two potential problems have been evaluated in this study. Fifty patients with a radical tumour resection were included, of whom 30 showed a p53 mutation in the primary tumour. Histopathologically tumour-free surgical margins were quantitatively analysed for mutated p53 by molecular diagnosis (plaque assay) and subsequent (immuno)histopathology. p53 mutated DNA was detected in the surgical margins of 19130 patients. Ininumohistochemistry, confirmed the presence of small tumour foci in 2/19 mutated p53-positive cases. In 7/19 cases, the tumour-specific p53 mutation was found in unresected dysplastic mucosal precursor lesions. Moreover, in a number of cases small p53-immunostained patches were detected, but the mutations found were never tumour-related. By screening contralateral exfoliated cells and plaque assays on RNA it was shown that detection of mutated-p53 DNA is prone to false-positive results. In conclusion, using p53 mutations as a marker, both MRC and unresected mutated p53-positive mucosal precursor lesions are detected within surgical margins. Molecular assessment of surgical margins using p53 mutations enables the selection of HNSCC patients at high risk for tumour recurrence, but tumour RNA seems at present to be a more specific biomolecule for analysis than tumour DNA. (C) Copyright 2002 John Wiley Sons, Ltd.