S S Murthy1, S J Rajappa2, S D Gundimeda1, K M Mallavarapu2, S Ayyagari2, P Yalavarthi2, D Fonseca1, P Paliwal2, Hgr Nair1, V Koppula3, Kvvn Raju4, S T Rao4. 1. Department of Pathology and Laboratory Medicine, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, Telangana, India. 2. Department of Medical Oncology, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, Telangana, India. 3. Department of Radiology, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, Telangana, India. 4. Department of Surgical Oncology, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, Telangana, India.
Abstract
BACKGROUND AND OBJECTIVES: Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) have shown good concordance for the detection of echinoderm microtubule-associated protein-like 4 and anaplastic lymphoma kinase (ALK) rearrangement. Since studies reporting FISH/IHC concordance, clinicopathological features, and clinical outcomes of ALK-positive patients from India are lacking, this study was undertaken. MATERIALS AND METHODS: This is a retrospective, observational study of patients with adenocarcinoma of the lung on whom ALK test was performed between March 2013 and December 2015. ALK status was assessed in 341 patients by FISH using Vysis ALK Dual Color Break Apart Rearrangement Probe and IHC using ALK D5F3 clone. Clinicopathological features were noted. Patients were managed as per the standard guidelines. Clinical outcomes - response rate (RR) and progression-free survival (PFS) - were measured. RESULTS: ALK rearrangement was positive in 37 patients (10.9%). ALK positivity was observed more commonly in younger patients with no predilection for any gender or any specific histological subtype. ALK by IHC was highly sensitive (100%), compared to FISH with concordance rate of 94.4%. Thirty one of thirty seven (31 of 37) patients received therapy of which 3 patients received palliative chemotherapy and 28 patients received tyrosine kinase inhibitors (crizotinib/ceritinib). Overall RR observed was 77.4%, and median PFS had not been reached at a median follow-up of 12.5 months. INTERPRETATION AND CONCLUSIONS: We report higher frequency of ALK positivity (10.9%) in patients with adenocarcinoma of the lung. ALK by IHC is more sensitive than FISH for ALK detection with high concordance. These patients had good clinical outcome with TKIs targeting ALK fusion protein.
BACKGROUND AND OBJECTIVES: Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) have shown good concordance for the detection of echinoderm microtubule-associated protein-like 4 and anaplastic lymphoma kinase (ALK) rearrangement. Since studies reporting FISH/IHC concordance, clinicopathological features, and clinical outcomes of ALK-positive patients from India are lacking, this study was undertaken. MATERIALS AND METHODS: This is a retrospective, observational study of patients with adenocarcinoma of the lung on whom ALK test was performed between March 2013 and December 2015. ALK status was assessed in 341 patients by FISH using Vysis ALK Dual Color Break Apart Rearrangement Probe and IHC using ALK D5F3 clone. Clinicopathological features were noted. Patients were managed as per the standard guidelines. Clinical outcomes - response rate (RR) and progression-free survival (PFS) - were measured. RESULTS:ALK rearrangement was positive in 37 patients (10.9%). ALK positivity was observed more commonly in younger patients with no predilection for any gender or any specific histological subtype. ALK by IHC was highly sensitive (100%), compared to FISH with concordance rate of 94.4%. Thirty one of thirty seven (31 of 37) patients received therapy of which 3 patients received palliative chemotherapy and 28 patients received tyrosine kinase inhibitors (crizotinib/ceritinib). Overall RR observed was 77.4%, and median PFS had not been reached at a median follow-up of 12.5 months. INTERPRETATION AND CONCLUSIONS: We report higher frequency of ALK positivity (10.9%) in patients with adenocarcinoma of the lung. ALK by IHC is more sensitive than FISH for ALK detection with high concordance. These patients had good clinical outcome with TKIs targeting ALK fusion protein.
Authors: Nikhil Suresh Ghadyalpatil; Avinash Pandey; Iyer Krishnamani; Chilukuri Srinivas; Shabnam J Rafiq; Sachin S Hingmire; Nagarjuna Maturu; Ragotham Reddy; Kiran K Kumar; K Sreekanth; Bharath Chandra Gurram; P M Parikh Journal: South Asian J Cancer Date: 2019 Apr-Jun