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

Saumya SHUKLA; Rahul Kumar PANDEY; Surya KANT; Rajiv GARG; Nidhi ANAND; Ram Awadh Singh KUSHWAHA; Kiran Preet MALHOTRA; Anand SRIVASTAVA; Madan Lal Brahma BHATT; Nuzhat HUSAIN

doi:10.5146/tjpath.2018.01438

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2019, Volume 35, Number 1, Page(s) 036-045

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DOI: 10.5146/tjpath.2018.01438

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

Saumya SHUKLA¹, Rahul Kumar PANDEY¹, Surya KANT², Rajiv GARG², Nidhi ANAND¹, Ram Awadh Singh KUSHWAHA², Kiran Preet MALHOTRA¹, Anand SRIVASTAVA², Madan Lal Brahma BHATT³, Nuzhat HUSAIN¹

¹Department of Pathology, Dr. Ram Manohar Lohia Institute of Medical Sciences, LUCKNOW, UP-INDIA
²Department of Respiratory Medicine, King George’s Medical University, LUCKNOW, UP-INDIA
³Department of Radiation Oncology, King George’s Medical University, LUCKNOW, UP-INDIA

Keywords: Non-small cell lung carcinoma, ALK re-arrangement, Fluorescence in situ hybridization, Immunohistochemistry

Objective: Predictive and prognostic markers have revolutionized personalized therapy in non-small cell lung carcinoma (NSCLC). Crizotinib is now approved for locally advanced or metastatic NSCLC that is anaplastic lymphoma kinase (ALK) positive by either Fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC). The current study aimed to detect the incidence of ALK gene re-arrangement in the Indian population, to compare the various IHC antibodies with FISH as a gold standard, and to analyze the morphology of cases with ALK phenotype.

Material and Method: A case series of 614 cases of NSCLC were included. IHC for detection of ALK phenotype was compared with FISH using 5A4 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 presence of mucin or signet ring cells in association with necrosis, high tumour grade and poor differentiation. Comparison of various antibody clones used in IHC revealed that the sensitivity and specificity using the D5F3 clone (100%, 100%) and 5A4 clone (87.5%, 100%) were similar while the ALK-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 D5F3 clone and 5A4 clone may be considered as a rapid reliable and inexpensive method for detection of ALK gene rearrangement.

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