Reliability of chromogenic in situ hybridization for detecting HER-2 gene status in breast cancer:: comparison with fluorescence in situ hybridization and assessment of interobserver reproducibility
Reliability of chromogenic in situ hybridization for detecting HER-2 gene status in breast cancer:: comparison with fluorescence in situ hybridization and assessment of interobserver reproducibility
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DOI：
10.1038/modpathol.3800432
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发表时间：
2005-08-01
期刊：
影响因子：
7.5
通讯作者：
Sneige, N
中科院分区：
文献类型：
--
作者：
Gong, Y;Gilcrease, M;Sneige, N
准确测定HER-2状态在乳腺癌患者的管理中非常重要，特别是在确定其是否适合接受曲妥珠单抗治疗时。荧光原位杂交技术（FISH）被认为是检测HER-2基因扩增的金标准方法。最近，显色原位杂交（CISH），其中HER-2是通过过氧化物酶反应检测和基因拷贝是由定期明场显微镜确定，已成为一个潜在的替代FISH。然而，该方法在应用于临床实践之前需要验证。在这项研究中，我们评估了80例浸润性乳腺癌的CISH，比较结果与FISH，并评估三个观察者之间的重复性。我们发现，在73例（91%）病例中，三位病理学家对CISH确定的HER-2状态达成一致，所有这些病例的结果均与相应的FISH结果相匹配：54例未扩增，19例扩增。在19例扩增的病例中，13例被一致评分为高水平扩增; 6例有轻微的评分差异（即低水平与高水平扩增）。一个主要的评分差异（即，nonamplification与扩增）被发现在其余7例，其中3例扩增，其中4例nonamplified FISH。后两个病例有17号染色体多体性。导致评分困难的病例是在高背景下具有不明确或边界信号的病例。总体而言，CISH和相应的FISH结果之间几乎完全一致，并且三位病理学家对CISH结果的解释具有高度重现性。我们的结论是，在一般情况下，HER-2状态可以可靠地评估CISH。在CISH拷贝数不明确或处于临界值的情况下，建议进行特异性FISH。
Accurate determination of HER-2 status is important in the management of patients with breast cancer, especially in determining their eligibility for trastuzumab therapy. Fluorescence in situ hybridization ( FISH) has been regarded as the gold standard method for detecting HER-2 gene amplification. Recently, chromogenic in situ hybridization (CISH), in which HER-2 is detected by a peroxidase reaction and the gene copies are determined by regular bright-field microscopy, has emerged as a potential alternative to FISH. However, this method requires validation before it can be adopted into clinical practice. In this study, we evaluated 80 cases of invasive breast carcinoma by CISH, compared the results with those obtained by FISH, and assessed interobserver reproducibility among three observers. We found that agreement among the three pathologists on the CISH-determined HER-2 status was achieved in 73 cases (91%), all of which had results matching the corresponding FISH results: 54 nonamplified and 19 amplified. Of the 19 amplified cases, 13 were scored unanimously as high-level amplification; six had a minor scoring discrepancy (ie, low-level vs high-level amplification). A major scoring discrepancy ( ie, nonamplification vs amplification) was found in the remaining seven cases, three of which were amplified and four of which were nonamplified by FISH. Two of the latter cases had a polysomy of chromosome 17. The cases that caused scoring difficulty were those with an equivocal or borderline signal number against a high background. Overall, there was nearly perfect agreement between the CISH and corresponding FISH results, and interpretation of CISH results were highly reproducible among the three pathologists. We conclude that, in general, HER-2 status can be reliably assessed by CISH. Confirmatory FISH is recommended in cases with equivocal or borderline CISH copy numbers.