Estrogen receptor alpha (ER alpha) mRNA copy numbers in immunohistochemically ER alpha-positive-, and negative breast cancer tissues.
Estrogen receptor alpha (ER alpha) mRNA copy numbers in immunohistochemically ER alpha-positive-, and negative breast cancer tissues.
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DOI：
10.1186/1471-2407-7-56
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发表时间：
2007-03-28
期刊：
影响因子：
3.8
通讯作者：
Yue Q
中科院分区：
文献类型：
--
作者：
Poola I;Yue Q
ERα的存在是用靶向分子疗法治疗乳腺癌患者的基础，靶向分子疗法阻断雌激素对乳腺癌细胞分裂的刺激。为了选择上述治疗的患者，目前，在临床实验室中通过对进行免疫组织化学（IHC）的载玻片进行显微镜评分来确定乳腺癌组织中ERα的存在。这种方法不定量，主观性强，需要大量的肿瘤组织，因此不能应用于立体定向和超声引导活检样本。为了解决这些问题，我们以前开发了基于定量实时PCR的分子检测方法，该方法可用于测定肿瘤样品中微微克量总RNA中ERα mRNA的拷贝数。然而，目前尚不清楚mRNA拷贝数与IHC阳性和阴性状态的相关性。本研究采用定量RTPCR方法检测了经1）免疫组化和2）功能性雌激素结合试验（functional estrogen binding assay）分级为ERα阳性和阴性的乳腺癌组织中ERα mRNA的拷贝数，并对数据进行统计学分析。我们在此证明，在通过IHC和配体结合试验分级为阳性的组织中，ERα mRNA拷贝数没有显著差异。我们在此建立了GAPDH的切割值为5 × 106拷贝/1010个mRNA拷贝，比值比为39.4，灵敏度为0.81，特异性为0.90，在乳腺癌组织中，通过IHC和雌激素结合试验，ERα蛋白阴性。ROC分析的数据得到的曲线下面积为0.8967。我们预计，此处确定的临界值对于在临床实验室中应用分子测定代替IHC以评价ERα的存在以用于预后和治疗目的具有高度意义。
The presence of ERα is the basis for treating breast cancer patients with targeted molecular therapies that block estrogen stimulation of breast cancer cell division. To select patients for the above therapies, currently, the ERα presence in breast cancer tissues is determined in clinical laboratories by microscopically scoring the slides subjected to immunohistochemistry (IHC). This method is not quantitative, highly subjective and requires large amount of tumor tissue, therefore, cannot be applied to sterotactic and ultrasound guided biopsy samples. To circumvent these problems, we previously developed quantitative real-time PCR based molecular assay that can be applied to determine mRNA copies of ERα in picogram amounts of total RNA from tumor samples. However, it is not known how the mRNA copy numbers correlate to IHC positive and negative status. In the current study we determined the copy numbers of ERα mRNA by Q RTPCR in breast cancer tissues that were graded as ERα-positive and negative by 1) IHC and 2) functional estrogen binding assay and statistically analyzed the data. We demonstrate here that ERα mRNA copy numbers are not significantly different in tissues that are graded as positive by IHC and ligand binding assays. We establish here a cut of value of 5 × 106 copies per 1010 mRNA copies of GAPDH with an Odds Radio of 39.4, Sensitivity of 0.81 and Specificity of 0.90 in breast cancer tissues that are negative for ERα protein by IHC and estrogen binding assays. ROC analysis of the data gave an area of 0.8967 under the curve. We expect that the cut off values determined here will be highly significant for applying molecular assay in the place of IHC in clinical laboratories for evaluating the presence of ERα for prognostic and therapeutic purposes.
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影响因子：
8.4
作者：
Jarzabek, K;Koda, M;Wolczynski, S
通讯作者：
Wolczynski, S
影响因子：
3.7
作者：
Poola, I
通讯作者：
Poola, I
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2.9
作者：
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通讯作者：
Hankins, WD
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作者：
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通讯作者：
CHAMBON, P
影响因子：
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作者：
Poola, I;Fuqua, SAW;Liu, AY
通讯作者：
Liu, AY