Detection of Anaplastic Lymphoma Kinase Gene Re-Arrangement in Non-Small Cell Lung Carcinoma in the Indian Population: Comparison of Techniques and Immunohistochemistry Clones

Abstract

Objective: Predictive and prognostic markers have revolutionized personalized therapy in non-small cell lung carcinoma (NSCLC). Crizotinibis now approved for locally advanced or metastatic NSCLC that is anaplastic lymphoma kinase (ALK) positive by either Fluorescence in situhybridization (FISH) or immunohistochemistry (IHC). The current study aimed to detect the incidence of ALK gene re-arrangement in theIndian population, to compare the various IHC antibodies with FISH as a gold standard, and to analyze the morphology of cases with ALKphenotype.Material and Method: A case series of 614 cases of NSCLC were included. IHC for detection of ALK phenotype was compared with FISH using5A4 clone (Labvision, USA), ALK-1(Dako, Denmark) and D5F3 clone (Ventana, USA).Results: ALK gene rearrangement was evident in 4.07% of the cases. Cases with ALK phenotype had unique histomorphology with presenceof mucin or signet ring cells in association with necrosis, high tumour grade and poor differentiation. Comparison of various antibody clonesused in IHC revealed that the sensitivity and specificity using the D5F3 clone (100%, 100%) and 5A4 clone (87.5%, 100%) were similar while theALK-1 clone had the lowest sensitivity and specificity (50%, 95.5%).Conclusion: The incidence of ALK gene rearrangement in NSCLC in the current Indian study is within the worldwide reported range of 3-5%.This is the first study from the Indian subcontinent to compare various IHC antibodies used for detection of ALK phenotype. IHC using D5F3clone and 5A4 clone may be considered as a rapid reliable and inexpensive method for detection of ALK gene rearrangement.