Too Sensitive or Just Right?: A Comparison of Two ALK Antibodies (D5F3 and ALK1) for Assessment of Anaplastic Large Cell Lymphoma. Issue 2 (28th April 2022)

• Record Type: Journal Article
• Authors: Martin, Dana; Smith, Steven C; Chesney, Alden; Jackson-Cook, Colleen; Pillappa, Raghavendra
• Is Part Of: American journal of clinical pathology. Volume 158:Issue 2(2022)
• Page Start: 283
• Page End: 290
• Publication Date: 2022-04-28
• Subjects: Anaplastic lymphoma kinase -- ALK -- Anaplastic large cell lymphoma -- ALCL -- Immunohistochemistry -- IHC -- Fluorescence in situ hybridization -- FISH; Diagnosis, Laboratory -- Periodicals; Pathology -- Periodicals; 616.07
• DOI: 10.1093/ajcp/aqac043
• Languages: English
• ISSNs: 0002-9173

Abstract

Abstract: Objectives: To compare the performance of the rabbit monoclonal antihuman CD246 antibody (D5F3 clone) with the established ALK1 clone for immunohistochemical assessment of anaplastic large cell lymphoma (ALCL). Methods: Archival cases of ALCL (n = 27) were assessed immunohistochemically by use of ALK1 and D5F3 clones under standard Clinical Laboratory Improvement Amendments–compliant conditions. The intensity of cytoplasmic staining (0 = none; 1 = faint; 2 = moderate; 3+ = strong) and proportion of neoplastic cells (0%, <5%, 5%-50%, >50%) were evaluated and compared with clinical ALK break-apart fluorescence in situ hybridization (FISH) assays. Results: Nine ALCL specimens were positive for ALK expression by ALK1 staining (33%; 1 = 1+; 0 = 2+; 8 = 3+), while 14 were positive by D5F3 staining (48%; 3 = 1+; 1 = 2+; 10 = 3+). Across the cohort, D5F3 staining showed a significantly greater proportion of cells staining positive ( P = .02) and greater intensity ( P = .03). Of 3 cases positive for D5F3 only with FISH results, none showed rearrangements, although 1 showed copy number gains at the ALK locus in a subset of cells. Conclusions: Overall, D5F3 showed greater stain intensity and proportion staining than ALK1 in ALK-positive ALCL cases, which is especially helpful in limited samples. Caution and consideration of orthogonal ALK testing types is recommended, especially for cases with weak or focal staining.