p53 家族蛋白在结直肠腺瘤和癌中的差异表达：预后和预测价值。

Differential expression of p53 family proteins in colorectal adenomas and carcinomas: Prognostic and predictive values.

机构信息

Pathology Department, National Cancer Institute, Cairo University, Cairo, Egypt.

Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt.

出版信息

Histol Histopathol. 2014 Feb;29(2):207-16. doi: 10.14670/HH-29.207. Epub 2013 Sep 2.

DOI:10.14670/HH-29.207

PMID:23996743

Abstract

BACKGROUND

We studied the contribution of p53 family proteins and their isoforms to the development and progression of colorectal carcinoma in relation to VEGF.

METHODS

p53, p63, p73 and VEGF proteins were assessed in 45 colorectal adenomas (CRAs), 80 carcinomas (CRCs) and 36 normal colonic tissue samples (NCT) by immunohistochemistry. Different p63 and p73 isoforms were assessed by RT-PCR. Aberrant protein and RNA expressions were correlated to patients' characteristics, disease free and overall survival (DFS and OS).

RESULTS

p53, p63, p73 and VEGF proteins were detected in 22.2%, 73.3%, 33.3%, 46.7% CRAs; in 68.8%, 38.8%, 62.5%, 62.5% CRCs and 16.7%, 83.3%; 13.9%, 41.7% NCT (p<0.05 except for VEGF). Commonest isoforms were TAp63α, ΔNp63, TAp73α in CRA and ΔNp63, TAp63α, ΔNp73, TAp73β in CRC. Significant correlations were found between aggressive tumor phenotypes and aberrations in p73, p53, p63, VEGF. DFS correlated with advanced stage, p73 and VEGF aberrations. While advanced stage, positive lymph nodes, p73 and p53 correlated with OS. Prognosis was worse in patients with aberrant p63 and p73 than in those with normal p63 and p73 expression regardless of p53 gene status (p⟨0.05).

CONCLUSIONS

p53 family proteins and VEGF play a pivotal role in colorectal carcinogenesis. p53 prognostic potential is augmented by p73 and p63 aberrations indicating a synergistic effect between the three family members. Nodal status, stage, p73, VEGF and p53 could be used as predictors of DFS and OS.

摘要

背景

我们研究了 p53 家族蛋白及其同工型在与 VEGF 相关的结直肠腺癌（CRC）发生和进展中的作用。

方法

通过免疫组化检测 45 例结直肠腺瘤（CRA）、80 例结直肠癌（CRC）和 36 例正常结肠组织（NCT）中的 p53、p63、p73 和 VEGF 蛋白。通过 RT-PCR 检测不同的 p63 和 p73 同工型。异常蛋白和 RNA 表达与患者特征、无病生存和总生存（DFS 和 OS）相关。

结果

在 CRA 中检测到 p53、p63、p73 和 VEGF 蛋白的比例分别为 22.2%、73.3%、33.3%和 46.7%；在 CRC 中为 68.8%、38.8%、62.5%和 62.5%；在 NCT 中为 16.7%、83.3%、13.9%和 41.7%（p<0.05，除 VEGF 外）。最常见的同工型为 CRA 中的 TAp63α、ΔNp63、TAp73α和 CRC 中的 ΔNp63、TAp63α、ΔNp73、TAp73β。p73、p53、p63、VEGF 的异常与侵袭性肿瘤表型存在显著相关性。DFS 与晚期、p73 和 VEGF 异常相关。而晚期、阳性淋巴结、p73 和 p53 与 OS 相关。p63 和 p73 异常的患者预后较 p63 和 p73 正常的患者差，无论 p53 基因状态如何（p<0.05）。