Detection of ALK Gene Rearrangement in Non-small Cell Lung Cancer: A Comparison of Fluorescence In Situ Hybridization and Chromogenic In Situ Hybridization with Correlation of ALK Protein Expression

Kim, Hyojin; Yoo, Seol Bong; Choe, Ji Young; Paik, Jin Ho; Xu, Xianhua; Nitta, Hiroaki; Zhang, Wenjun; Grogan, Thomas M.; Lee, Choon Taek; Jheon, Sanghoon; Chung, Jin Haeng

doi:10.1097/jto.0b013e31821cfc73

Cited by 148 publications

(111 citation statements)

References 20 publications

Supporting

Mentioning

103

Contrasting

Unclassified

Order By: Relevance

“…The use of rt-pcr, immunohistochemistry, and chromogenic in-situ hybridization has also been described in clinical samples with variable sensitivity 51,52 . Several studies have addressed the role of immunohistochemistry in the detection of ALK-positive cases.…”

Section: Alk Gene Rearrangementsmentioning

confidence: 99%

The Role of Molecular Pathology in Non-Small-Cell Lung Carcinoma—Now and in the Future

2012

View full text Add to dashboard Cite

In recent years, better understanding of the molecular biology of non-small-cell lung carcinoma (nsclc) has led to a revolution in the work-up of these neoplasms. As a pathology diagnosis, "nsclc" without further attempt at subclassification is no longer accepted as a standard of care; separating squamous cell carcinoma from adenocarcinoma and large-cell carcinoma carries implications for prognosis and treatment decisions. Currently, detection of the presence in nsclc of mutations involving the epidermal growth factor receptor (EGFR) gene and fusion of the N-terminal portion of the protein encoded by EML4 (echinoderm microtubule-associated protein-like 4 gene) with the intracellular signaling portion of the receptor tyrosine kinase encoded by ALK (anaplastic lymphoma kinase gene)-that is, EML4-ALK-and variants has become routine in many centres because patients having tumours harbouring such alterations might benefit from tyrosine kinase inhibitors as part of their treatment regimen.The purpose of the present review is to highlight important aspects of the screening for molecular derangements in nsclc and to briefly discuss the emergence of possible future biomarkers.

show abstract

Section: Alk Gene Rearrangementsmentioning

confidence: 99%

The Role of Molecular Pathology in Non-Small-Cell Lung Carcinoma—Now and in the Future

2012

View full text Add to dashboard Cite

show abstract

“…Microscopic analysis was performed with an Olympus BX41 epifluorescence microscope and a charge-coupled device camera (Cohu, San Diego, CA, USA) interfaced with the CytoVision system (software version 3.9; Applied Imaging, Pittsburg, PA, USA). To avoid misinterpretation due to artifacts, the distance between two separated signals of the break-apart probe was estimated using the two times of biggest signal size (Kim et al 2006).…”

Section: Fish Analysismentioning

confidence: 99%

Assessing RET/PTC in thyroid nodule fine-needle aspirates: the FISH point of view

Caria¹,

Dettori²,

Frau³

et al. 2013

Endocrine-Related Cancer

View full text Add to dashboard Cite

RET/PTC rearrangement and BRAF V600E mutation are the two prevalent molecular alterations associated with papillary thyroid carcinoma (PTC), and their identification is increasingly being used as an adjunct to cytology in diagnosing PTC. However, there are caveats associated with the use of the molecular approach in fine-needle aspiration (FNA), particularly for RET/PTC, that should be taken into consideration. It has been claimed that a clonal or sporadic presence of this abnormality in follicular cells can distinguish between malignant and benign nodules. Nevertheless, the most commonly used PCR-based techniques lack the capacity to quantify the number of abnormal cells. Because fluorescence in situ hybridization (FISH) is the most sensitive method for detecting gene rearrangement in a single cell, we compared results from FISH and conventional RT-PCR obtained in FNA of a large cohort of consecutive patients with suspicious nodules and investigated the feasibility of setting a FISH-FNA threshold capable of distinguishing non-clonal from clonal molecular events. For this purpose, a home brew break-apart probe, able to recognize the physical breakage of RET, was designed. While a R3% FISH signal for broken RET was sufficient to distinguish nodules with abnormal follicular cells, only samples with a R6.8% break-apart FISH signal also exhibited positive RT-PCR results. On histological analysis, all nodules meeting the R6.8% threshold proved to be malignant. These data corroborate the power of FISH when compared with RT-PCR in quantifying the presence of RET/PTC in FNA and validate the RT-PCR efficiency in detecting clonal RET/PTC alterations.

show abstract

“…Although most authors consider a reaction of 2þ and 3þ as positive with good correlation with FISH results, the definition of a positive result varies among studies. 9,16,17,46,50 In some studies a reaction of 1þ is considered positive, 9,46,50 whereas in others a 1þ reaction is considered inconclusive and is followed by FISH testing, 51,52 and in a recent study of the FDA-approved assay, 1þ was considered negative. 26 Reports of weak reactivity are more likely due to preanalytic factors such as fixation and antigen retrieval, as well as the clone and detection system used, rather than different levels of fusion protein expression.…”

Section: Alk Antibodiesmentioning

confidence: 99%

Lung Carcinoma Predictive Biomarker Testing by Immunoperoxidase Stains in Cytology and Small Biopsy Specimens: Advantages and Limitations

Zhou

Moreira²

2016

Archives of Pathology &Amp; Laboratory Medicine

View full text Add to dashboard Cite

Context.-In the burgeoning era of molecular genomics, immunoperoxidase (IPOX) testing grows increasingly relevant as an efficient and effective molecular screening tool. Patients with lung carcinoma may especially benefit from the use of IPOX because most lung carcinomas are inoperable at diagnosis and only diagnosed by small tissue biopsy or fine-needle sampling. When such small specimens are at times inadequate for molecular testing, positive IPOX results still provide actionable information.Objective.-To describe the benefits and pitfalls of IPOX in the detection of biomarkers in lung carcinoma cytology specimens and small biopsies by summarizing the currently available commercial antibodies, preanalytic variables, and analytic considerations.Data Sources.-PubMed.Conclusions.-Commercial antibodies exist for IPOX detection of aberrant protein expression due to EGFR L858R mutation, EGFR E746_A750 deletion, ALK rearrangement, ROS1 rearrangement, and BRAF V600E mutation, as well as PD-L1 expression in tumor cells. Automated IPOX protocols for ALK and PD-L1 detection were recently approved by the Food and Drug Administration as companion diagnostics for targeted therapies, but consistent interpretive criteria remain to be elucidated, and such protocols do not yet exist for other biomarkers. The inclusion of cytology specimens in clinical trials would expand patients' access to testing and treatment, yet there is a scarcity of clinical trial data regarding the application of IPOX to cytology, which can be attributed to trial designers' lack of familiarity with the advantages and limitations of cytology. The content of this review may be used to inform clinical trial design and advance IPOX validation studies.

show abstract

Detection of ALK Gene Rearrangement in Non-small Cell Lung Cancer: A Comparison of Fluorescence In Situ Hybridization and Chromogenic In Situ Hybridization with Correlation of ALK Protein Expression

Cited by 148 publications

References 20 publications

The Role of Molecular Pathology in Non-Small-Cell Lung Carcinoma—Now and in the Future

The Role of Molecular Pathology in Non-Small-Cell Lung Carcinoma—Now and in the Future

Assessing RET/PTC in thyroid nodule fine-needle aspirates: the FISH point of view

Lung Carcinoma Predictive Biomarker Testing by Immunoperoxidase Stains in Cytology and Small Biopsy Specimens: Advantages and Limitations

Contact Info

Product

Resources

About