Concordance of Immunohistochemistry and Fluorescence In Situ Hybridization in the Detection of Anaplastic Lymphoma Kinase (ALK) and Ros Proto-oncogene 1 (ROS1) Gene Rearrangements in Non-Small Cell Lung Carcinoma: A 4.5-Year Experience Highlighting Challenges and Pitfalls.

Autor:	Nambirajan A; From the Departments of Pathology (Nambirajan, Sood, Khatoon, Jain), Medical Oncology (Malik), and Pulmonary, Critical Care and Sleep Medicine (Mohan), All India Institute of Medical Sciences (AIIMS), New Delhi, India., Sood R; From the Departments of Pathology (Nambirajan, Sood, Khatoon, Jain), Medical Oncology (Malik), and Pulmonary, Critical Care and Sleep Medicine (Mohan), All India Institute of Medical Sciences (AIIMS), New Delhi, India., Khatoon W; From the Departments of Pathology (Nambirajan, Sood, Khatoon, Jain), Medical Oncology (Malik), and Pulmonary, Critical Care and Sleep Medicine (Mohan), All India Institute of Medical Sciences (AIIMS), New Delhi, India., Malik PS; From the Departments of Pathology (Nambirajan, Sood, Khatoon, Jain), Medical Oncology (Malik), and Pulmonary, Critical Care and Sleep Medicine (Mohan), All India Institute of Medical Sciences (AIIMS), New Delhi, India., Mohan A; From the Departments of Pathology (Nambirajan, Sood, Khatoon, Jain), Medical Oncology (Malik), and Pulmonary, Critical Care and Sleep Medicine (Mohan), All India Institute of Medical Sciences (AIIMS), New Delhi, India., Jain D; From the Departments of Pathology (Nambirajan, Sood, Khatoon, Jain), Medical Oncology (Malik), and Pulmonary, Critical Care and Sleep Medicine (Mohan), All India Institute of Medical Sciences (AIIMS), New Delhi, India.
Jazyk:	angličtina
Zdroj:	Archives of pathology & laboratory medicine [Arch Pathol Lab Med] 2024 Aug 01; Vol. 148 (8), pp. 928-937.
DOI:	10.5858/arpa.2023-0229-OA
Abstrakt:	Context.—: ALK and ROS1 rearrangements are essential biomarkers to be tested in advanced lung adenocarcinomas. While D5F3 Ventana assay is a companion diagnostic for anaplastic lymphoma kinase-targeted therapy, immunohistochemistry is only a screening tool for detecting ROS1 rearrangement. Confirmation by cytogenetic or molecular techniques is necessary. Objective.—: To evaluate the utility of ALK and ROS1 fluorescence in situ hybridization as a complement to immunohistochemistry in routine predictive biomarker testing algorithms. Design.—: The study was ambispective, spanning 4.5 years during which lung adenocarcinoma samples were subjected to EGFR mutation testing by real-time polymerase chain reaction and ALK/ROS1 rearrangement testing by immunohistochemistry (Ventana D5F3 assay for anaplastic lymphoma kinase protein; manual assay with D4D6 clone for Ros proto-oncogene 1 protein). Fluorescence in situ hybridization was performed in all anaplastic lymphoma kinase equivocal and Ros proto-oncogene 1 immunopositive cases. Results.—: Of 1874 samples included, EGFR mutations were detected in 27% (481 of 1796). Anaplastic lymphoma kinase immunohistochemistry was positive in 10% (174 of 1719) and equivocal in 3% (58 of 1719) of samples tested. ALK fluorescence in situ hybridization showed 81% (77 of 95) concordance with immunohistochemistry. Ros proto-oncogene 1 immunopositivity was noted in 13% (190 of 1425) of cases, with hybridization-confirmed rearrangements in 19.3% (26 of 135) of samples, all of which showed diffuse, strong- to moderate-intensity, cytoplasmic staining in tumor cells. Ros proto-oncogene 1 protein overexpression without rearrangement was significantly common in EGFR-mutant and ALK-rearranged adenocarcinomas. Conclusions.—: Immunostaining is a robust method for ALK-rearrangement testing, with fluorescence in situ hybridization adding value in the rare equivocal stained case. ROS1-rearrangement testing is more cost-effective if immunohistochemistry is followed by fluorescence in situ hybridization after excluding EGFR-mutant and ALK-rearranged adenocarcinomas. (© 2024 College of American Pathologists.)
Databáze:	MEDLINE
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