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评估头颈部鳞状细胞癌患者肿瘤细胞和组织学正常黏膜中的 p53 功能活性。

Assessment of p53 functional activity in tumor cells and histologically normal mucosa from patients with head and neck squamous cell carcinoma.

机构信息

Center for Applied Molecular Technologies, Institute for Experimental and Clinical Research, Université Catholique de Louvain, Brussels, Belgium.

出版信息

Head Neck. 2012 Nov;34(11):1542-50. doi: 10.1002/hed.21960. Epub 2011 Nov 23.

DOI:10.1002/hed.21960
PMID:22109999
Abstract

BACKGROUND

The purpose of this study was to investigate the value of p53 functional analysis of separated alleles in yeast (FASAY) as a witness of p53/p21 pathway alteration in head and neck squamous cell carcinoma (HNSCC).

METHODS

The p53 transcriptional activity was prospectively analyzed in 82 newly diagnosed patients with HNSCC. FASAY and p53 immunostaining were carried out on paired tumoral and histologically normal tissues. The predictive value of FASAY for locoregional recurrence was assessed by Cox survival analysis.

RESULTS

Loss of p53/p21 transcriptional activity was encountered in 88% tumoral and 18% histologically normal samples, associated with mutations (79%) and insertions/deletions (21%). The p53 overexpression underestimated p53 transcriptional abnormalities. FASAY-positive histologically normal mucosa was significantly associated with locoregional recurrence.

CONCLUSION

FASAY positivity indicates field cancerization in a subgroup of patients with HNSCC, in which nonfunctional p53 was significantly associated with locoregional recurrence. This prompted us to pursue the study on the p53 functional status of normal mucosa in patients with HNSCC.

摘要

背景

本研究旨在探讨酵母中分离等位基因的 p53 功能分析(FASAY)作为头颈部鳞状细胞癌(HNSCC)中 p53/p21 通路改变的见证物的价值。

方法

前瞻性分析 82 例新诊断的 HNSCC 患者的 p53 转录活性。对配对的肿瘤和组织学正常组织进行 FASAY 和 p53 免疫染色。Cox 生存分析评估 FASAY 对局部区域复发的预测价值。

结果

88%的肿瘤组织和 18%的组织学正常样本存在 p53/p21 转录活性丧失,与突变(79%)和插入/缺失(21%)相关。p53 过表达低估了 p53 转录异常。FASAY 阳性的组织学正常黏膜与局部区域复发显著相关。

结论

FASAY 阳性表明 HNSCC 患者亚组存在区域性癌变,其中无功能 p53 与局部区域复发显著相关。这促使我们继续研究 HNSCC 患者正常黏膜中 p53 的功能状态。

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