Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Diagnostic Pathology
Published in: Diagnostic Pathology 1/2016

Open Access 01-12-2016 | Case Report

Next-generation sequencing facilitates detection of the classic E13-A20 EML4-ALK fusion in an ALK-FISH/IHC inconclusive biopsy of a stage IV lung cancer patient: a case report

Authors: Anna-Lena Volckmar, Volker Endris, Farastuk Bozorgmehr, Clemens Lier, Carlota Porcel, Martina Kirchner, Jonas Leichsenring, Roland Penzel, Michael Thomas, Peter Schirmacher, Arne Warth, Albrecht Stenzinger

Published in: Diagnostic Pathology | Issue 1/2016

Login to get access

Abstract

Background

Inhibition of the oncogenic fusion-gene EML4-ALK is a current first-line approach for patients with stage IV non-small cell lung cancer. While FISH was established as the gold standard for identifying these patients, there is accumulating evidence that other methods of detection, i.e., immunohistochemistry and next-generation sequencing (NGS), exist that may be equally successful. However, the concordance of these methods is under investigation.

Case presentation

Adding to the current literature, we here report a 56 year old female never-smoker with stage IV lung adenocarcinoma whose biopsy was IHC and FISH inconclusive but positive in NGS. Retroactive profiling of the resection specimen corroborated fusion reads obtained by NGS, FISH-positivity and showed weak ALK-positivity by IHC. Consequently, we diagnosed the case as ALK-positive rendering the patient eligible to crizotinib treatment.

Conclusions

With IHC on biopsy material only, this case would have been overlooked withholding effective therapy.
Literature
1.
Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 2007;448:561–6.CrossRefPubMed
2.
Kwak EL, Bang Y-J, Camidge DR, Shaw AT, Solomon B, Maki RG, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010;363:1693–703.CrossRefPubMedPubMedCentral
3.
Shaw AT, Kim D-W, Nakagawa K, Seto T, Crino L, Ahn M-J, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013;368:2385–94.CrossRefPubMed
4.
Solomon BJ, Mok T, Kim D-W, Wu Y-L, Nakagawa K, Mekhail T, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014;371:2167–77.CrossRefPubMed
5.
Christensen JG, Zou HY, Arango ME, Li Q, Lee JH, McDonnell SR, et al. Cytoreductive antitumor activity of PF-2341066, a novel inhibitor of anaplastic lymphoma kinase and c-Met, in experimental models of anaplastic large-cell lymphoma. Mol Cancer Ther. 2007;6:3314–22.CrossRefPubMed
6.
Conklin CMJ, Craddock KJ, Have C, Laskin J, Couture C, Ionescu DN. Immunohistochemistry is a reliable screening tool for identification of ALK rearrangement in non-small-cell lung carcinoma and is antibody dependent. J Thorac Oncol. 2013;8:45–51.CrossRefPubMed
7.
Paik JH, Choe G, Kim H, Choe J-Y, Lee HJ, Lee C-T, et al. Screening of anaplastic lymphoma kinase rearrangement by immunohistochemistry in non-small cell lung cancer: correlation with fluorescence in situ hybridization. J Thorac Oncol. 2011;6:466–72.CrossRefPubMed
8.
Park HS, Lee JK, Kim D-W, Kulig K, Kim TM, Lee S-H, et al. Immunohistochemical screening for anaplastic lymphoma kinase (ALK) rearrangement in advanced non-small cell lung cancer patients. Lung Cancer. 2012;77:288–92.CrossRefPubMed
9.
McLeer-Florin A, Moro-Sibilot D, Melis A, Salameire D, Lefebvre C, Ceccaldi F, et al. Dual IHC and FISH testing for ALK gene rearrangement in lung adenocarcinomas in a routine practice: a French study. J Thorac Oncol. 2012;7:348–54.CrossRefPubMed
10.
Wynes MW, Sholl LM, Dietel M, Schuuring E, Tsao MS, Yatabe Y, et al. An international interpretation study using the ALK IHC antibody D5F3 and a sensitive detection kit demonstrates high concordance between ALK IHC and ALK FISH and between evaluators. J Thorac Oncol. 2014;9:631–8.CrossRefPubMedPubMedCentral
11.
Rosoux A, Pauwels P, Duplaquet F, D’Haene N, Weynand B, Delos M, et al. Effectiveness of crizotinib in a patient with ALK IHC-positive/FISH-negative metastatic lung adenocarcinoma. Lung Cancer. 2016;98:118–21.CrossRefPubMed
12.
Peled N, Palmer G, Hirsch FR, Wynes MW, Ilouze M, Varella-Garcia M, et al. Next-generation sequencing identifies and immunohistochemistry confirms a novel crizotinib-sensitive ALK rearrangement in a patient with metastatic non-small-cell lung cancer. J Thorac Oncol. 2012;7:e14–6.CrossRefPubMedPubMedCentral
13.
Gagnier JJ, Kienle G, Altman DG, Moher D, Sox H, Riley D. The CARE guidelines: consensus-based clinical case reporting guideline development. BMJ Case Rep. 2013;2013. doi:10.​1136/​bcr-2013-201554.
14.
Taheri D, Zahavi DJ, Del Carmen Rodriguez M, Meliti A, Rezaee N, Yonescu R, et al. For staining of ALK protein, the novel D5F3 antibody demonstrates superior overall performance in terms of intensity and extent of staining in comparison to the currently used ALK1 antibody. Virchows Arch. 2016;469:345–50.CrossRefPubMed
15.
Mino-Kenudson M, Chirieac LR, Law K, Hornick JL, Lindeman N, Mark EJ, et al. A novel, highly sensitive antibody allows for the routine detection of ALK-rearranged lung adenocarcinomas by standard immunohistochemistry. Clin Cancer Res. 2010;16:1561–71.CrossRefPubMedPubMedCentral
16.
Pfarr N, Stenzinger A, Penzel R, Warth A, Dienemann H, Schirmacher P, et al. High-throughput diagnostic profiling of clinically actionable gene fusions in lung cancer. Genes Chromosomes Cancer. 2016;55:30–44.CrossRefPubMed
17.
Cancer Genome Atlas Research Network. Comprehensive molecular profiling of lung adenocarcinoma. Nature. 2014;511:543–50.
18.
von Laffert M, Stenzinger A, Hummel M, Weichert W, Lenze D, Warth A, et al. ALK-FISH borderline cases in non-small cell lung cancer: Implications for diagnostics and clinical decision making. Lung Cancer. 2015;90:465–71.CrossRef
19.
Lindeman NI, Cagle PT, Beasley MB, Chitale DA, Dacic S, Giaccone G, et al. Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. J Thorac Oncol. 2013;8:823–59.CrossRefPubMedPubMedCentral
20.
Cabillic F, Gros A, Dugay F, Begueret H, Mesturoux L, Chiforeanu DC, et al. Parallel FISH and immunohistochemical studies of ALK status in 3244 non-small-cell lung cancers reveal major discordances. J Thorac Oncol. 2014;9:295–306.CrossRefPubMed
21.
Pekar-Zlotin M, Hirsch FR, Soussan-Gutman L, Ilouze M, Dvir A, Boyle T, et al. Fluorescence in situ hybridization, immunohistochemistry, and next-generation sequencing for detection of EML4-ALK rearrangement in lung cancer. Oncologist. 2015;20:316–22.CrossRefPubMedPubMedCentral
22.
Conde E, Suarez-Gauthier A, Benito A, Garrido P, Garcia-Campelo R, Biscuola M, et al. Accurate identification of ALK positive lung carcinoma patients: novel FDA-cleared automated fluorescence in situ hybridization scanning system and ultrasensitive immunohistochemistry. PLoS One. 2014;9:e107200.CrossRefPubMedPubMedCentral
23.
Sholl LM, Weremowicz S, Gray SW, Wong K-K, Chirieac LR, Lindeman NI, Hornick JL. Combined use of ALK immunohistochemistry and FISH for optimal detection of ALK-rearranged lung adenocarcinomas. J Thorac Oncol. 2013;8:322–8.CrossRefPubMedPubMedCentral
24.
von Laffert M, Warth A, Penzel R, Schirmacher P, Kerr KM, Elmberger G, et al. Multicenter immunohistochemical ALK-testing of non-small-cell lung cancer shows high concordance after harmonization of techniques and interpretation criteria. J Thorac Oncol. 2014;9:1685–92.CrossRef
Metadata
Title
Next-generation sequencing facilitates detection of the classic E13-A20 EML4-ALK fusion in an ALK-FISH/IHC inconclusive biopsy of a stage IV lung cancer patient: a case report
Authors
Anna-Lena Volckmar
Volker Endris
Farastuk Bozorgmehr
Clemens Lier
Carlota Porcel
Martina Kirchner
Jonas Leichsenring
Roland Penzel
Michael Thomas
Peter Schirmacher
Arne Warth
Albrecht Stenzinger
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2016
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/s13000-016-0581-4

Other articles of this Issue 1/2016

Diagnostic Pathology 1/2016 Go to the issue

Retraction Note

Retraction note: Up-regulation of miR-130b expression level and down-regulation of miR-218 serve as potential biomarker in the early detection of human osteosarcoma

Research

Rare subtype(s) and frequency of multi-viral subtype high-risk human papilloma virus infection in high-grade squamous intraepithelial lesion and squamous cell carcinoma in a cervical carcinoma prevalent developing country: a multiplex real-time polymerase chain reaction-based pilot study

Research

Multiplexed automated digital quantification of fusion transcripts: comparative study with fluorescent in-situ hybridization (FISH) technique in acute leukemia patients

Research Article

The findings of CT and MRI in patients with metanephric adenoma

Case Report

Intraosseous inflammatory myofibroblastic tumor of the mandible with a novel ATIC-ALK fusion mutation: a case report

Research

Quantitative comparison and reproducibility of pathologist scoring and digital image analysis of estrogen receptor β2 immunohistochemistry in prostate cancer