Detection of ALK Rearrangement by Immunohistochemistry in Lung Adenocarcinoma and the Identification of a Novel EML4-ALK Variant

Abstract

IHC can effectively detect ALK rearrangement in lung cancer. It might provide a reliable and cost-effective diagnostic approach in routine pathologic laboratories for the identification of suitable candidates for ALK-targeted therapy.

Screening for ALK in non-small cell lung carcinomas: 5A4 and D5F3 antibodies perform equally well, but combined use with FISH is recommended

“…True discrepancies between ALK IHC and Page 19 of 29 A c c e p t e d M a n u s c r i p t 19 FISH findings rarely exist and response to Crizotinib has been documented in both IHC+/FISH-and IHC-/FISH+ carcinomas [12,15,[24][25][26]. Several institutions have already implemented ALK screening by IHC with systematic confirmatory FISH of only the IHCpositive carcinomas [8,27,28].…”

Diagnosis of EML4 - ALK Translocation With FISH, Immunohistochemistry, and Real-time Polymerase Chain Reaction in Patients With Non–Small Cell Lung Cancer

“…However, alternative antibodies such as 5A4 (Abcam, Novacastra, Newcastle, UK) and D5F3 (Cell Signaling Technology, Danvers, MA) have shown promising results. 20 Of the 22 known different EML4-ALK translocation variants, 15 the most common are as follows: 1 (49.6%), 3a/b (25.6%), and variant 2 (10%). 29 Fusions with TFG, KIF5B, KLCL1, and PTPN3 have also been described.…”

“…Current methods available are fluorescence in situ hybridization (FISH), which identifies genetic translocations 16,17 ; reverse transcriptase polymerase chain reaction (RT-PCR), which detects fusion transcripts 18 ; and immunohistochemistry (IHC), in which a monoclonal antibody is used to detect aberrant ALK protein expression. 19,20 Presently, the only diagnostic test for ALK rearrangements in NSCLC approved by the US FDA is FISH and consists of a break-apart probe manufactured by Abbot Molecular. 21,22 The Ventana ALK (D5F3) IHC assay uses a D5F3 rabbit monoclonal primary antibody and detects rearrangements with 100% sensitivity and 98% specificity.…”

Primary lung cancer with metastasis to the ipsilateral breast-a case report

“…It defines a unique subgroup of lung ADC, which may be responsive to ALK inhibitors. 42 Cytokeratin 5 is a protein marker which defines a basal-like subtype of invasive ductal carcinoma of the breast that is usually CK5/6+, ER-, PR-, HER2-. 43 CK5 was negative in our case.…”