A comparison of <i><scp>ALK</scp></i> gene rearrangement and <scp>ALK</scp> protein expression in primary lung carcinoma and matched metastasis

Bittar, Humberto E. Trejo; Luvison, Alyssa; Miller, Caitlyn; Đačić, Sanja

doi:10.1111/his.13215

Cited by 11 publications

(11 citation statements)

References 46 publications

(134 reference statements)

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“…ALK IHC was performed on freshly cut 4‐μm thick formalin‐fixed paraffin‐embedded tissue sections using the Ventana ALK (D5F3) CDx assay. The anti‐ALK (D5F3 clone) rabbit monoclonal antibody was applied on a BenchMark XT autostainer with the Ultraview diaminobenzidine detection kit (Ventana Medical Systems Inc, Tucson, AZ, USA) . Staining was interpreted clinically as positive if tumor cells showed a moderate or strong multifocal or diffuse expression.…”

Section: Methodsmentioning

confidence: 99%

Comprehensive analysis of age‐related somatic mutation profiles in Chinese young lung adenocarcinoma patients

Yang

et al. 2019

Cancer Medicine

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Background Lung adenocarcinoma in young adults is a rare entity with the oncogenic genetic alterations associated being poorly understood. In the present study, the effect of genetic alterations in lung adenocarcinoma patients diagnosed in young patients is reported. Methods Twenty young lung adenocarcinoma patients (age years: median: 33.5, range: 24‐36) were enrolled in the current study and 24 patients who were at common age of the disease onset (age years: median: 61.5, range: 52‐79) were selected for comparison. Paraffin sections of lung adenocarcinoma were analyzed using the whole‐exome sequencing platform. Results Similar number of somatic mutations per tumor were found in the young patients and their older counterparts. Although no age‐related differences were detected in the numbers of lung adenocarcinoma patients harboring well‐known gene variants, mutations in FRG1 and KMT2C were associated with a younger age especially after correcting for tobacco smoking and sex (FRG1: P = 0.027, KMT2C: P = 0.046). Five genetic variants showed higher alteration frequencies in young patients compared to the unclassified East Asian population, suggesting these mutations as disease‐related hereditary germline variants. Conclusions These results suggest different characteristics of lung adenocarcinoma between the young and the patients at common age of onset. Young patients with lung adenocarcinoma have a distinctly unique prevalence of oncogenic genetic alterations.

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Section: Methodsmentioning

confidence: 99%

Comprehensive analysis of age‐related somatic mutation profiles in Chinese young lung adenocarcinoma patients

Yang

et al. 2019

Cancer Medicine

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“…FISH does not detect all ALK rearrangements and certain complex rearrangements reduce the distance between the two FISH probes, which can give a false negative FISH image [ 46 ]. Aside from the difference in sensitivity and specificity the discord can sometimes be explained by the intra- and inter-tumor heterogeneity in terms of the ALK status, in particular when comparing IHC/ICC or FISH and methods using direct extraction of RNA without prior visual control of the lesion [ 49 , 101 , 102 ]. Certain isoforms of ALK arise from a mechanism of alternative initiation of transcription giving protein expression that is not ALK -positive with FISH [ 103 ].…”

Section: Methods For Detection Of An Alk Rearramentioning

confidence: 99%

ALK in Non-Small Cell Lung Cancer (NSCLC) Pathobiology, Epidemiology, Detection from Tumor Tissue and Algorithm Diagnosis in a Daily Practice

Hofman

2017

Cancers

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Patients with advanced-stage non-small cell lung carcinoma (NSCLC) harboring an ALK rearrangement, detected from a tissue sample, can benefit from targeted ALK inhibitor treatment. Several increasingly effective ALK inhibitors are now available for treatment of patients. However, despite an initial favorable response to treatment, in most cases relapse or progression occurs due to resistance mechanisms mainly caused by mutations in the tyrosine kinase domain of ALK. The detection of an ALK rearrangement is pivotal and can be done using different methods, which have variable sensitivity and specificity depending, in particular, on the quality and quantity of the patient’s sample. This review will first highlight briefly some information regarding the pathobiology of an ALK rearrangement and the epidemiology of patients harboring this genomic alteration. The different methods used to detect an ALK rearrangement as well as their advantages and disadvantages will then be examined and algorithms proposed for detection in daily routine practice.

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“… 43 , 44 In addition, comparable expression of ALK protein by D5F3 IHC between samples from primary and metastatic sites has also been well documented with concordance rates of 94%–100%. 71 – 73 …”

Section: Ihc With D5f3mentioning

confidence: 99%

ALK (D5F3) CDx: an immunohistochemistry assay to identify ALK-positive NSCLC patients

Uruga¹,

Mino‐Kenudson²

2018

PGPM

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Screening for anaplastic lymphoma kinase (ALK) rearrangements is a very important process in treatment decision making for advanced non-small-cell lung cancer (NSCLC). Although fluorescent in situ hybridization (FISH) is considered the universally accepted reference standard, it is associated with technical difficulties and high costs that have made global implementation of this assay challenging. Conversely, ALK immunohistochemistry has shown high sensitivity and specificity compared to FISH and other molecular assays and is more cost-effective. In fact, the ALK (D5F3) CDx immunohistochemistry assay was approved by the US Food and Drug Administration as a standalone test for ALK rearrangements in lung cancer in 2015. In this review, we will discuss the overview of ALK rearrangements in NSCLC, various testing methods for ALK rearrangements, and the details of immunohistochemistry for ALK, in particular one with the ALK antibody clone D5F3.

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A comparison of ALK gene rearrangement and ALK protein expression in primary lung carcinoma and matched metastasis

Cited by 11 publications

References 46 publications

Comprehensive analysis of age‐related somatic mutation profiles in Chinese young lung adenocarcinoma patients

Comprehensive analysis of age‐related somatic mutation profiles in Chinese young lung adenocarcinoma patients

ALK in Non-Small Cell Lung Cancer (NSCLC) Pathobiology, Epidemiology, Detection from Tumor Tissue and Algorithm Diagnosis in a Daily Practice

ALK (D5F3) CDx: an immunohistochemistry assay to identify ALK-positive NSCLC patients

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