Department of Computational Science and Artificial Intelligence, University of Granada, ES-18071 Granada, Spain. cuadroslujan @ yahoo.es
Pathobiology. 2010;77(1):38-45. doi: 10.1159/000272953. Epub 2010 Feb 25.
The Her2/neu status is of great clinical value in breast tumor patients. Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) techniques are the test of choice for many practicing pathologies. The main objective of this retrospective study was to investigate the relationship between Her2/neu breast cancer amplification and overexpression (DNA, mRNA and protein).
To accomplish this goal, we evaluated Her2/neu mRNA expression by real-time quantitative RT-PCR, gene amplification by FISH and protein expression by IHC.
An excellent correlation between FISH and IHC Her2/neu results was observed, confirming that protein levels were directly related to DNA amplification. Polysomy 17 was frequently found in tumors showing Her2/neu overexpression. However, we did not find any statistically significant correlation among DNA, mRNA and protein levels, suggesting that Her2/neu could be post-transcriptionally regulated.
There was a highagreement between Her2/neu gene amplification and protein overexpression but not mRNA expression levels. Nevertheless, IHC3+ and FISH-positive tumors indicated higher expression levels of Her2/neu mRNA by RT-PCR than those observed in IHC and FISH-negative tumors. These findings question the relevance of quantitative RT-PCR in routine assessment of Her2/neu overexpression in human breast cancer in the clinical laboratory setting.
Her2/neu 状态在乳腺肿瘤患者中具有重要的临床价值。荧光原位杂交（FISH）和免疫组织化学（IHC）技术是许多临床病理的首选检测方法。本回顾性研究的主要目的是研究 Her2/neu 乳腺癌扩增与过表达（DNA、mRNA 和蛋白质）之间的关系。
为了实现这一目标，我们通过实时定量 RT-PCR 评估 Her2/neu mRNA 表达，通过 FISH 评估基因扩增，通过 IHC 评估蛋白质表达。
观察到 FISH 和 IHC Her2/neu 结果之间存在极好的相关性，证实蛋白质水平与 DNA 扩增直接相关。在 Her2/neu 过表达的肿瘤中经常发现 17 号染色体三体。然而，我们没有发现 DNA、mRNA 和蛋白质水平之间存在任何统计学上的显著相关性，表明 Her2/neu 可能受到转录后调控。
Her2/neu 基因扩增与蛋白过表达之间具有高度一致性，但与 mRNA 表达水平不一致。然而，IHC3+和 FISH 阳性肿瘤的 Her2/neu mRNA 表达水平通过 RT-PCR 高于 IHC 和 FISH 阴性肿瘤。这些发现质疑在临床实验室环境中，定量 RT-PCR 在常规评估人类乳腺癌 Her2/neu 过表达中的相关性。
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