scholarly journals Fluorescence in Situ Hybridization (FISH) for Detecting Anaplastic Lymphoma Kinase (ALK) Rearrangement in Lung Cancer: Clinically Relevant Technical Aspects

2019 ◽  
Vol 20 (16) ◽  
pp. 3939 ◽  
Author(s):  
Zhenya Tang ◽  
Lu Wang ◽  
Guilin Tang ◽  
L. Jeffrey Medeiros
Keyword(s):  
Lung Cancer ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Simultaneous Detection ◽  
The United States ◽  
Driver Mutations ◽  
Alk Rearrangement ◽  
Technical Aspects ◽  
Anaplastic Lymphoma

In 2011, the Vysis Break Apart ALK fluorescence in situ hybridization (FISH) assay was approved by the United States Food and Drug Administration as a companion diagnostic for detecting ALK rearrangement in lung cancer patients who may benefit from treatment of tyrosine kinase inhibitor therapy. This assay is the current “gold standard”. According to updated ALK testing guidelines from the College of American Pathologists, the International Association for the Study of Lung Cancer and the Association for Molecular Pathology published in 2018, ALK immunohistochemistry is formally an alternative to ALK FISH, and simultaneous detection of multiple hot spots, including, at least, ALK, ROS1, RET, MET, ERBB2, BRAF and KRAS genes is also recommended while performing next generation sequencing (NGS)-based testing. Therefore, ALK status in a specimen can be tested by different methods and platforms, even in the same institution or laboratory. In this review, we discuss several clinically relevant technical aspects of ALK FISH, including pros and cons of the unique two-step (50- to 100-cell) analysis approach employed in the Vysis Break Apart ALK FISH assay, including: the preset cutoff value of ≥15% for a positive result; technical aspects and biology of discordant results obtained by different methods; and incidental findings, such as ALK copy number gain or amplification and co-existent driver mutations. These issues have practical implications for ALK testing in the clinical laboratory following the updated guidelines.

scholarly journals Discordance between Fluorescence In Situ Hybridization and Immunohistochemistry Analysis of Anaplastic Lymphoma Kinase Rearrangement in Indian Patients with Non-Small Cell Lung Cancer

2020 ◽  
Vol 9 (02) ◽  
pp. 109-114
Author(s):  
Manish Kumar ◽  
Kishore Kumar ◽  
Harinder Pal Singh ◽  
Suresh Nair ◽  
Amol Patel ◽  
...  
Keyword(s):  
Lung Cancer ◽  
In Situ Hybridization ◽  
Pleural Effusion ◽  
Brain Metastasis ◽  
Fluorescence In Situ Hybridization ◽  
Cell Lung Cancer ◽  
Anaplastic Lymphoma Kinase ◽  
Alk Rearrangement ◽  
Anaplastic Lymphoma

Abstract Aims This study aims to evaluate the incidence of anaplastic lymphoma kinase (ALK) mutation in nonsmall cell lung cancer (NSCLC) incorporating fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) methods and to look for any discordance. Methods We evaluated 101 samples obtained from an enriched cohort of NSCLCs patients from the Army Hospital Research and Referral, New Delhi, India, between November 2016 and November 2018. IHC was performed using the highly-sensitive D5F3 rabbit monoclonal primary antibody. FISH was performed with dual-color, break-apart probe (ZytoLight SPEC) on formalin-fixed, and paraffin-embedded tissue. Discordance between IHC and FISH for ALK rearrangements was evaluated. Pearson correlation coefficient (r) was performed to identify any association of ALK presence (by IHC and FISH) with smoking brain metastasis, programmed death-ligand (PD-L1) expression, pleural effusion, and histopathological subtype. Results A total of 7.92% (8/101) cases tested by IHC and 9.9% (10/101) cases tested by FISH were positive for ALK rearrangement. Of 93 ALK IHC-negative cases, 4 were ALK FISH-positive, whereas of 91 ALK FISH-negative cases, 4 were ALK IHC-positive cases. The correlation analysis demonstrated no or very weak correlation in ALK mutations by IHC or FISH with smoking, brain metastasis, PD-L1 expression, pleural effusion, and histopathological examination, except a weak positive correlation (r = 0.33) observed between brain metastasis and ALK rearrangement identified by FISH. Conclusions Our study demonstrated a somewhat similar incidence of ALK FISH-positive cases and ALK IHC-positive cases, though the incidence was numerically higher for ALK-FISH method.

scholarly journals Fluorescence In Situ Hybridization, Immunohistochemistry, and Next‐Generation Sequencing for Detection of EML4‐ALK Rearrangement in Lung Cancer

2015 ◽  
Vol 20 (3) ◽  
pp. 316-322 ◽  
Author(s):  
Marina Pekar‐Zlotin ◽  
Fred R. Hirsch ◽  
Lior Soussan‐Gutman ◽  
Maya Ilouze ◽  
Addie Dvir ◽  
...  
Keyword(s):  
Lung Cancer ◽  
In Situ Hybridization ◽  
Next Generation Sequencing ◽  
Fluorescence In Situ Hybridization ◽  
Next Generation ◽  
Alk Rearrangement ◽  
Generation Sequencing

scholarly journals Heterogeneous Tumor-Immune Microenvironments between Primary and Metastatic Tumors in a Patient with ALK Rearrangement-Positive Large Cell Neuroendocrine Carcinoma

2020 ◽  
Vol 21 (24) ◽  
pp. 9705
Author(s):  
Takahiro Tashiro ◽  
Kosuke Imamura ◽  
Yusuke Tomita ◽  
Daisuke Tamanoi ◽  
Akira Takaki ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Neuroendocrine Carcinoma ◽  
Large Cell ◽  
Large Cell Neuroendocrine Carcinoma ◽  
Driver Mutations ◽  
Single Individual ◽  
Alk Rearrangement ◽  
Metastatic Tumors ◽  
Anaplastic Lymphoma ◽  
Metastatic Lesions

Evolution of tumor-immune microenviroments (TIMEs) occurs during tumor growth and dissemination. Understanding inter-site tumor-immune heterogeneity is essential to harness the immune system for cancer therapy. While the development of immunotherapy against lung cancer with driver mutations and neuroendocrine tumors is ongoing, little is known about the TIME of large cell neuroendocrine carcinoma (LCNEC) or anaplastic lymphoma kinase (ALK) rearrangement-positive lung cancer. We present a case study of a 32-year-old female patient with ALK-rearrangement-positive LCNEC, who had multiple distant metastases including mediastinal lymph-node, bilateral breasts, multiple bones, liver and brain. Multiple biopsy samples obtained from primary lung and three metastatic tumors were analyzed by fluorescent multiplex immunohistochemistry. Tissue localizations of tumor-infiltrating lymphocytes in the tumor nest and surrounding stroma were evaluated. T cell and B cell infiltrations were decreased with distance from primary lung lesion. Although each tumor displayed a unique TIME, all tumors exhibited concomitant regression after treatment with an ALK-inhibitor. This study provides the first evidence of the coexistence of distinct TIME within a single individual with ALK-rearrangement-positive LCNEC. The present study contributes to our understanding of heterogeneous TIMEs between primary and metastatic lesions and provides new insights into the complex interplay between host-immunity and cancer cells in primary and metastatic lesions.

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