Kim Gruber1, Martin Kohlhäufl, Godehard Friedel, German Ott, Claudia Kalla. 1. *Department of Clinical Pathology, Robert-Bosch-Krankenhaus and Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany; and ‡Center for Pulmonology and Thoracic Surgery, Klinik Schillerhöhe, Gerlingen, Stuttgart, Germany.
Abstract
INTRODUCTION: Successful treatment of lung cancer patients with crizotinib depends on the accurate diagnosis of anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearrangements. The approved fluorescence in-situ hybridization test is complex and difficult to use in daily diagnostic practice. Immunohistochemical assays-rapid and perfectly adapted for routine pathology practice-have been proposed as alternatives. We evaluated the novel high affinity ALK 1A4 antibody for routine diagnostics in formalin fixed, paraffin-embedded tumor specimens. METHODS: Detection of ALK protein expression was investigated by comparing the new 1A4 antibody and the established D5F3 antibody/Ventana system in 218 lung cancer specimens with known ALK status preanalyzed by quantitative reverse transcription-polymerase chain reaction and fluorescence in-situ hybridization (20 ALK-positive cases, 198 ALK-negative cases). RESULTS: The accuracy of both immunohistochemical assays for the detection of ALK rearrangements was high. Using a conventional staining procedure without signal enhancement, the 1A4 antibody assay identified all 20 ALK-rearranged tumors (100% sensitivity) and correctly characterized 196 of 198 negative cases (99.1% specificity). The D5F3/Ventana assay detected 19 ALK-rearranged tumors and typed 217 of 218 tumors correctly (95% sensitivity, 99.5 % specificity). CONCLUSIONS: The novel 1A4 antibody represents a promising candidate for screening lung tumors for the presence of ALK rearrangements.
INTRODUCTION: Successful treatment of lung cancerpatients with crizotinib depends on the accurate diagnosis of anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearrangements. The approved fluorescence in-situ hybridization test is complex and difficult to use in daily diagnostic practice. Immunohistochemical assays-rapid and perfectly adapted for routine pathology practice-have been proposed as alternatives. We evaluated the novel high affinity ALK 1A4 antibody for routine diagnostics in formalin fixed, paraffin-embedded tumor specimens. METHODS: Detection of ALK protein expression was investigated by comparing the new 1A4 antibody and the established D5F3 antibody/Ventana system in 218 lung cancer specimens with known ALK status preanalyzed by quantitative reverse transcription-polymerase chain reaction and fluorescence in-situ hybridization (20 ALK-positive cases, 198 ALK-negative cases). RESULTS: The accuracy of both immunohistochemical assays for the detection of ALK rearrangements was high. Using a conventional staining procedure without signal enhancement, the 1A4 antibody assay identified all 20 ALK-rearranged tumors (100% sensitivity) and correctly characterized 196 of 198 negative cases (99.1% specificity). The D5F3/Ventana assay detected 19 ALK-rearranged tumors and typed 217 of 218 tumors correctly (95% sensitivity, 99.5 % specificity). CONCLUSIONS: The novel 1A4 antibody represents a promising candidate for screening lung tumors for the presence of ALK rearrangements.
Authors: M von Laffert; P Schirmacher; A Warth; W Weichert; R Büttner; R M Huber; J Wolf; F Griesinger; M Dietel; C Grohé Journal: Pathologe Date: 2016-03 Impact factor: 1.011
Authors: Philipp Jurmeister; Claudia Vollbrecht; Korinna Jöhrens; Daniela Aust; Anke Behnke; Albrecht Stenzinger; Roland Penzel; Volker Endris; Peter Schirmacher; Annette Fisseler-Eckhoff; Jens Neumann; Thomas Kirchner; Reinhard Büttner; Sabine Merkelbach-Bruse; Hans Kreipe; Danny Jonigk; Wolfram Jochum; Regulo Rodriguez; Manfred Dietel; David Horst; Michael Hummel; Maximilian von Laffert Journal: Virchows Arch Date: 2021-06-25 Impact factor: 4.064