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原发性肺腺癌中通过荧光原位杂交(FISH)检测的ALK重排频率及其与ALK免疫组化的相关性

Frequency of ALK Rearrangement by FISH Testing and its Correlation with ALK-IHC in Adenocarcinoma of Primary Lung Origin.

作者信息

Moatter Samar, Anwar Namrah, Moatter Tariq, Pervez Shahid

机构信息

Section of Histopathology, Department of Pathology and Laboratory Medicine, Aga Khan University Hospital, Karachi, Pakistan. Email:

出版信息

Asian Pac J Cancer Prev. 2018 Jun 25;19(6):1735-1738. doi: 10.22034/APJCP.2018.19.6.1735.

DOI:10.22034/APJCP.2018.19.6.1735
PMID:29938474
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6103595/
Abstract

Anaplastic lymphoma kinase (ALK) gene can be oncogenic either by forming fusion with other genes, amplification of the gene or by having mutations. ALK rearrangement can either be detected by standard “fluorescence in situ hybridization (FISH)” or “immunohistochemistry (IHC)”. Objective of this study was to record the prevalence of ALK rearrangement in adenocarcinoma of Primary Lung origin and compare it with ALK-IHC staining. Data of 64 patients of lung adenocarcinoma from 2015-2017 was analyzed. All of the FFPE biopsies were tested for EGFR (qPCR) followed by ALK rearrangement (by FISH and IHC) on EGFR negative samples. Out of 64 samples, 21.8% (14) showed EGFR mutations and 14% (7/50) were positive for ALK rearrangement when checked by FISH. In IHC testing for ALK (FISH positive) 8% (4/50) showed positivity. In conclusion ALK-FISH positive cases are higher than other studies likely due to the relatively small sample size. FISH testing was found to be more sensitive than IHC; one reason may be the low level of ALK. Our study warrants that currently FISH remains the gold standard for screening of ALK gene rearrangements.

摘要

间变性淋巴瘤激酶(ALK)基因可通过与其他基因形成融合、基因扩增或发生突变而具有致癌性。ALK重排可通过标准的“荧光原位杂交(FISH)”或“免疫组织化学(IHC)”检测。本研究的目的是记录原发性肺腺癌中ALK重排的发生率,并将其与ALK免疫组化染色结果进行比较。分析了2015年至2017年64例肺腺癌患者的数据。对所有福尔马林固定石蜡包埋活检组织进行表皮生长因子受体(EGFR)检测(定量聚合酶链反应),然后对EGFR阴性样本进行ALK重排检测(FISH和IHC)。在64个样本中,21.8%(14个)显示EGFR突变,FISH检测时14%(7/50)的样本ALK重排呈阳性。在ALK免疫组化检测(FISH阳性)中,8%(4/50)呈阳性。总之,ALK-FISH阳性病例高于其他研究,可能是由于样本量相对较小。发现FISH检测比IHC更敏感;一个原因可能是ALK水平较低。我们的研究表明,目前FISH仍然是筛查ALK基因重排的金标准。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77cb/6103595/f9ed6101a769/APJCP-19-1735-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77cb/6103595/257ba43b21f3/APJCP-19-1735-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77cb/6103595/f9ed6101a769/APJCP-19-1735-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77cb/6103595/257ba43b21f3/APJCP-19-1735-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77cb/6103595/f9ed6101a769/APJCP-19-1735-g002.jpg

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本文引用的文献

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J Thorac Oncol. 2015 Jun;10(6):e37-9. doi: 10.1097/JTO.0000000000000467.
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First-line crizotinib versus chemotherapy in ALK-positive lung cancer.克唑替尼对比化疗用于治疗 ALK 阳性肺癌。
N Engl J Med. 2014 Dec 4;371(23):2167-77. doi: 10.1056/NEJMoa1408440.
3
U.S. Food and Drug Administration approval: crizotinib for treatment of advanced or metastatic non-small cell lung cancer that is anaplastic lymphoma kinase positive.
美国食品和药物管理局批准:克唑替尼治疗间变性淋巴瘤激酶阳性的晚期或转移性非小细胞肺癌。
Clin Cancer Res. 2014 Apr 15;20(8):2029-34. doi: 10.1158/1078-0432.CCR-13-3077. Epub 2014 Feb 26.
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Atypical negative ALK break-apart FISH harboring a crizotinib-responsive ALK rearrangement in non-small-cell lung cancer.非小细胞肺癌中具有克唑替尼敏感性ALK重排的非典型阴性ALK断裂分离荧光原位杂交检测结果
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Clin Cancer Res. 2013 Aug 1;19(15):4273-81. doi: 10.1158/1078-0432.CCR-13-0318. Epub 2013 May 31.
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