A Novel, Highly Sensitive ALK Antibody 1A4 Facilitates Effective Screening for ALK Rearrangements in Lung Adenocarcinomas by Standard Immunohistochemistry

作者：Gruber Kim; Kohlhaeufl Martin; Friedel Godehard; Ott German; Kalla Claudia^*

来源：Journal of Thoracic Oncology, 2015, 10(4): 713-716.

DOI：10.1097/JTO.0000000000000427

• Lung adenocarcinoma
• ALK
• Immunohistochemistry
• Antibody 1A4
• Routine diagnostics

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.

• 出版日期2015-4