Her-2/neu expression in node-negative breast cancer: direct tissue quantitation by computerized image analysis and association of overexpression with increased risk of recurrent disease.
Her-2/neu expression in node-negative breast cancer: direct tissue quantitation by computerized image analysis and association of overexpression with increased risk of recurrent disease.
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发表时间：
1993-10
期刊：
影响因子：
11.2
通讯作者：
M. Press;M. Pike;V. Chazin;G. Hung;J. Udove;Mitchell Markowicz;J. Danyluk;W. Godolphin;M. Sliwkowski
中科院分区：
文献类型：
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作者：
M. Press;M. Pike;V. Chazin;G. Hung;J. Udove;Mitchell Markowicz;J. Danyluk;W. Godolphin;M. Sliwkowski
HER-2/neu原癌基因（也称为c-er B B-2）与表皮生长因子受体同源，但不同。淋巴结阳性乳腺癌中该基因的扩增已被证明与早期复发和较短的总生存期相关。在淋巴结阴性乳腺癌患者中，准确的预后数据可以对治疗决策做出重大贡献的亚组，HER-2/neu扩增和/或过表达的预后效用一直存在争议。本报告的目的是解决围绕这一争议的问题，并使用适当的表征试剂和方法，在一组仔细随访的患者中评估过表达的预后效用。在这份报告中，我们提出的数据从HER-2/neu表达的研究，专门设计来测试是否过度表达与淋巴结阴性乳腺癌复发的风险增加。从704名患有淋巴结阴性乳腺癌的女性中，有105名经历了复发性疾病（复发病例），在相同的随访期后，105名女性与105名无复发的女性（无疾病对照）相匹配。免疫组织化学用于评估复发病例及其匹配的无病对照的存档组织块中HER-2/neu的表达。重要的是，使用一系列分子表征的乳腺癌标本来确认所用抗体具有足够的灵敏度和特异性，以鉴定在该福尔马林固定的石蜡包埋组织队列中过表达HER-2/neu蛋白的那些癌症。此外，还开发了一种定量方法，以更准确地评估通过免疫染色肿瘤组织鉴定的HER-2/neu蛋白的量。这是使用在细菌表达载体中合成的纯化HER-2/neu蛋白和衍生自一系列细胞系的蛋白裂解物来完成的，所述细胞系被工程化以表达确定范围的HER-2/neu癌蛋白水平。通过使用具有确定表达水平的细胞作为校准材料，免疫组织化学染色的计算机图像分析可用于确定这些细胞系以及人乳腺癌标本中癌蛋白产物的量。通过免疫组织化学测定的计算机图像分析确定的HER-2/neu蛋白产物的量的定量与一系列分子表征的乳腺癌细胞系和乳腺癌组织标本的定量分析非常密切相关。（400字处截断摘要）
The HER-2/neu proto-oncogene (also known as c-erb B-2) is homologous with, but distinct from, the epidermal growth factor receptor. Amplification of this gene in node-positive breast cancers has been shown to correlate with both earlier relapse and shorter overall survival. In node-negative breast cancer patients, the subgroup for which accurate prognostic data could make a significant contribution to treatment decisions, the prognostic utility of HER-2/neu amplification and/or overexpression has been controversial. The purpose of this report is to address the issues surrounding this controversy and to evaluate the prognostic utility of overexpression in a carefully followed group of patients using appropriately characterized reagents and methods. In this report we present data from a study of HER-2/neu expression designed specifically to test whether or not overexpression is associated with an increased risk of recurrence in node-negative breast cancers. From a cohort of 704 women with node-negative breast cancer who experienced recurrent disease (relapsed cases) 105 were matched with 105 women with no recurrence (disease-free controls) after the equivalent follow-up period. Immunohistochemistry was used to assess HER-2/neu expression in archival tissue blocks from both relapsed cases and their matched disease-free controls. Importantly, a series of molecularly characterized breast cancer specimens were used to confirm that the antibody used was of sufficient sensitivity and specificity to identify those cancers overexpressing the HER-2/neu protein in this formalin-fixed, paraffin-embedded tissue cohort. In addition, a quantitative approach was developed to more accurately assess the amount of HER-2/neu protein identified by immunostaining tumor tissue. This was done using a purified HER-2/neu protein synthesized in a bacterial expression vector and protein lysates derived from a series of cell lines, engineered to express a defined range of HER-2/neu oncoprotein levels. By using cells with defined expression levels as calibration material, computerized image analysis of immunohistochemical staining could be used to determine the amount of oncoprotein product in these cell lines as well as in human breast cancer specimens. Quantitation of the amount of HER-2/neu protein product determined by computerized image analysis of immunohistochemical assays correlated very closely with quantitative analysis of a series of molecularly characterized breast cancer cell lines and breast cancer tissue specimens.(ABSTRACT TRUNCATED AT 400 WORDS)