Detection and quantitation of HER-2/neu gene amplification in human breast cancer archival material using fluorescence in situ hybridization.

Detection and quantitation of HER-2/neu gene amplification in human breast cancer archival material using fluorescence in situ hybridization.
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发表时间:
1996-07
期刊:
影响因子:
8
通讯作者:
G. Pauletti;W. Godolphin;M. Press;D. Slamon
G. Pauletti;W. Godolphin;M. Press;D. Slamon
中科院分区:
医学1区
文献类型:
--
作者:
G. Pauletti;W. Godolphin;M. Press;D. Slamon

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HER-2/neu基因的扩增和过表达发生在25-30%的人类乳腺癌中。这种基因改变与淋巴结阴性或淋巴结阳性乳腺癌妇女的临床预后不良有关。测试这种关联的最初研究有些争议,这种争议在很大程度上是由于在测试档案材料是否存在改变时使用的方法和/或试剂的显著异质性。这些方法包括许多用于DNA、RNA和蛋白质的固体基质印迹技术以及免疫组织化学。荧光原位杂交(FISH)代表了检测这种基因改变的最新方法。在这项研究中,FISH与Southern、Northern和Western blot分析以及免疫组织化学在大量存档的人类乳腺癌标本中进行了比较。在评估HER-2/ new扩增的福尔马林固定石蜡包埋材料时,发现FISH优于所有其他测试方法。这项研究的结果也证实了HER-2/neu在没有基因扩增的乳腺癌中很少发生过表达(约占病例的3%)。该方法在检测HER-2/neu基因扩增方面具有快速、重复性好、可靠性高的特点,具有临床应用价值。
Amplification and overexpression of the HER-2/neu gene occurs in 25-30% of human breast cancers. This genetic alteration is associated with a poor clinical prognosis in women with either node negative or node positive breast cancers. The initial studies testing this association were somewhat controversial and this controversy was due in large part to significant heterogeneity in both the methods and/or reagents used in testing archival material for the presence of the alteration. These methods included a number of solid matrix blotting techniques for DNA, RNA and protein as well as immunohistochemistry. Fluorescence in situ hybridization (FISH) represents the newest methodologic approach for testing for this genetic alteration. In this study, FISH is compared to Southern, Northern and Western blot analyses as well as immunohistochemistry in a large cohort of archival human breast cancer specimens. FISH was found to be superior to all other methodologies tested in assessing formalin fixed, paraffin embedded material for HER-2/neu amplification. The results from this study also confirm that overexpression of HER-2/neu rarely occurs in the absence of gene amplification in breast cancer (approximately 3% of cases). This method of analysis is rapid, reproducible and extremely reliable in detecting presence of HER-2/neu gene amplification and should have clinical utility.