High concordance between Immunohistochemistry and RT-PCR in diagnosing ALK rearrangement in lung adenocarcinoma cytologic samples

Introduction: Lung cancer, predominantly lung adenocarcinoma, remains a major health challenge in Indonesia, with late-stage detection being common. This study explores the use of quantitative real-time polymerase chain reaction (qRT-PCR) for assessing ALK rearrangement from smear samples, a significant shift towards less invasive diagnostic methods, by assessing its concordance with immunohistochemistry (IHC) in detecting Anaplastic Lymphoma Kinase (ALK) rearrangements in lung adenocarcinoma patients. Materials and Methods: This observational cross-sectional study analyzed 175 lung adenocarcinoma samples lacking EGFR mutations collected between 2018 and 2022. IHC was performed with the Ventana ALK D5F3 clone antibody on cell blocks or core needle biopsy specimens. The EML4-ALK fusion rearrangement status was determined using quantitative RNA qRT-PCR analysis on the smear specimen from transthoracic needle aspiration (TTNA) from the same sample. Only specimens with viable tumor cells were included, ensuring the exclusion of metastatic or necrotic samples. Results: ALK rearrangements were identified in 16.2 (23/142) of samples via IHC and 14.8 (21/142) via qRT-PCR. Prevalence did not significantly differ by age and sex. The study found a 98.5 concordance rate between the two methods, with a κ coefficient of 0.95 (95 CI, 0.91-0.98), indicating almost perfect agreement. Conclusion: The high concordance between IHC and qRT-PCR underscores their reliability in detecting ALK rearrangements, crucial for the precise diagnosis and treatment of lung adenocarcinoma in Indonesia. These findings support the use of either method, depending on available resources and expertise, to enhance lung cancer management. © 2025, Malaysian Medical Association. All rights reserved.