Relative quantification of ERBB2 mRNA in invasive duct carcinoma of the breast:: Correlation with ERBB-2 protein expression and ERBB2 gene copy number
Relative quantification of ERBB2 mRNA in invasive duct carcinoma of the breast:: Correlation with ERBB-2 protein expression and ERBB2 gene copy number
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DOI：
10.1078/0344-0338-00445
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发表时间：
2003-01-01
影响因子：
2.8
通讯作者：
Hilská, I
中科院分区：
文献类型：
--
作者：
Mrhalová, M;Kodet, R;Hilská, I
使用赫赛汀治疗患有乳腺人表皮生长因子受体2（ERBB - 2）蛋白阳性浸润性导管癌（IDC）的患者这一选择，需要精确确定ERBB2的状态。本研究的目的是评估ERBB2信使核糖核酸（mRNA）水平，重点关注ERBB - 2蛋白表达（免疫组化，IHC）与ERBB2基因拷贝数（荧光原位杂交，FISH）结果不一致的病例。对39例IDC（21例IHC和FISH结果一致，15例中度不一致，3例显著不一致）进行了研究。使用实时定量逆转录聚合酶链反应（Q - RT - PCR）测定ERBB2 mRNA的表达。ERBB - 2蛋白阴性且无ERBB2基因扩增的IDC具有较低的ERBB2 mRNA水平。蛋白3 +过度表达且基因强烈扩增（>10拷贝/肿瘤细胞）的病例，其ERBB2 mRNA表达显著增加。在15例中度差异的IDC中的13例（每一个肿瘤细胞最多10拷贝基因/ERBB - 2蛋白阴性；无扩增/蛋白2 +）中，mRNA水平较低，与ERBB - 2蛋白阴性且无ERBB2基因扩增的病例相当。在3例结果显著不一致的病例（基因扩增/蛋白阴性 - 1例；蛋白3 +/无扩增 - 2例）中，Q - RT - PCR结果在“正常”范围内。无效的基因扩增和蛋白积累是可能的解释。Q - RT - PCR显示有2例ERBB2 mRNA高表达且FISH和/或IHC结果不一致。转录效率提高（蛋白2 +/高mRNA/无基因扩增）以及联合失调（蛋白阴性/高mRNA/无扩增）是这些结果的可能原因。Q - RT - PCR似乎有助于阐明临界或不一致的IHC和FISH结果。
The option to treat patients suffering from ERBB-2 protein-positive invasive duct carcinomas of the breast (IDC) with Herceptin requires a precise determination of the ERBB2 status. The aim of the study was to evaluate the ERBB2 mRNA level, placing emphasis on cases with discordant findings between ERBB-2 protein expression (IHC) and a copy number of the ERBB2 gene (FISH). Thirty-nine IDCs (21 cases IHC and FISH concordant, 15 cases moderately discordant, 3 cases markedly discordant) were investigated. ERBB2 mRNA expression was determined using quantitative real-time RT-PCR (Q-RT-PCR). IDCs with negative ERBB-2 protein and without ERBB2 gene amplification had a low ERBB2 mRNA level. Cases with 3+ overexpression of the protein and with strong gene amplification (> 10 copies/tumor cell) had a significantly increased expression of ERBB2 mRNA. In 13 of 15 IDCs with moderate discrepancies (up to 10 copies of the gene per one tumor cell/negative ERBB-2 protein; without amplification/2+ protein) mRNA was low, comparable to that in cases with negative ERBB-2 protein and without ERBB2 gene amplification. In three cases with markedly discordant findings (the gene amplified/protein negative - one case; protein 3+/no amplification - 2 cases), Q-RT-PCR results were within a "normal" limit. Ineffective gene amplification and protein accumulation are suggested explanations. Q-RT-PCR revealed two cases with highly expressed ERBB2 mRNA and discordant FISH and/or IHC findings. Increased effectiveness of transcription (protein 2+/high mRNA/without the gene amplification), and combined dysregulation (protein negative/high mRNA/no amplification) are possible causes of these findings. Q-RT-PCR appears useful in clarifying borderline or discrepant IHC and FISH findings.