Assessment of c-erbB-2 amplification by immunohistochemistry in paraffin-embedded breast cancer.
Assessment of c-erbB-2 amplification by immunohistochemistry in paraffin-embedded breast cancer.
复制标题
通过免疫组织化学评估石蜡包埋乳腺癌中的 c-erbB-2 扩增。
作者：
B. Kerns;P. Jordan;G. Huper;J. Marks;J. Iglehart;L. J. Layfied
c-erbB-2（HER-2/neu）原癌基因在许多人类恶性肿瘤的发生和预后判断中具有重要意义。DNA（Southern）杂交和免疫印迹（Western）技术最常分别用于确定该原癌基因的扩增状态和蛋白质表达。这些提取技术通常是耗时的、昂贵的，并且取决于肿瘤的组织学特征而易变。另一方面，石蜡免疫组织化学（P-IHC）具有时间和成本效益。此外，由于分析的原位性质，这种技术可以提供比提取技术更高的灵敏度和特异性。在这里介绍的数据，同时评估67例人乳腺癌c-erbB-2基因拷贝数和癌蛋白表达的稀释DNA杂交和P-IHC，分别。在67例中的64例（95.5%）中，高水平表达与基因扩增相关，而未检测到表达与正常二倍体基因拷贝数相关。在3例不一致病例中的2例中，P-IHC预测的扩增未得到Southern分析的证实。在这些病例中，肿瘤肿块受到病变的导管内成分或标本内丰富的间质成分的限制。我们的结论是，P-IHC提供了一个有利的替代Southern分析在评估c-erbB-2基因拷贝数的这种癌蛋白在人类乳腺癌。此外，免疫组织化学可能被证明上级的提取技术在标本与有限的肿瘤质量，如活检材料，间质丰富的肿瘤，或早期病变，如导管内癌。
The c-erbB-2 (HER-2/neu) proto-oncogenes is important in oncogenesis and for determination of prognosis in a number of human malignancies. DNA (Southern) hybridization and immunoblotting (Western) techniques are most commonly utilized for determining amplification status and protein expression of this proto-oncogene, respectively. These extraction techniques are often time-consuming, costly, and subject to variability depending on the histological characteristics of the tumor. Paraffin-immunohistochemistry (P-IHC), on the other hand, is time and cost-effective. In addition, this technique may offer enhanced sensitivity and specificity over extraction techniques due to the in situ nature of analysis. In data presented here, 67 cases of human mammary carcinoma were concomitantly assessed for c-erbB-2 gene copy number and oncoprotein expression by dilutional DNA hybridization and P-IHC, respectively. In 64 (95.5%) of 67 cases, high level expression was associated with gene amplification, whereas no detectable expression was associated with a normal diploid gene copy number. In two of the three discrepant cases, P-IHC predicted amplification not corroborated by Southern analysis. In these cases, tumor mass was limited by the intraductal component of the lesion or by an abundance of stromal elements within the specimen. We conclude that P-IHC offers a favorable alternative to Southern analysis in the assessment of c-erbB-2 gene copy number of this oncoprotein in human mammary carcinoma. Furthermore, immunohistochemistry may prove superior to either extraction technique in specimens with limited tumor mass, such as biopsy materials, stroma-rich tumors, or early stage lesions such as intraductal carcinoma.