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Testing for ALK rearrangement in lung adenocarcinoma: a multicenter comparison of immunohistochemistry and fluorescent in situ hybridization

Abstract

Rearrangements of anaplastic lymphoma kinase (ALK) gene in non-small cell lung cancer (NSCLC) define a molecular subgroup of tumors characterized clinically by sensitivity to ALK tyrosine kinase inhibitors such as crizotinib. Although ALK rearrangements may be detected by reverse transcriptase-PCR, immunohistochemistry or fluorescence in situ hybridization (FISH), the optimal clinical strategy for identifying ALK rearrangements in clinical samples remains to be determined. We evaluated immunohistochemistry using three different antibodies (ALK1, 5A4 and D5F3 clones) to detect ALK rearrangements and compared those with FISH. We report the frequency and clinicopathologic features of lung cancers harboring ALK translocations in 594 resected NSCLCs (470 adenocarcinomas; 83 squamous carcinomas, 26 large cell carcinomas and 15 other histological subtypes) using a tissue microarray approach. We identified an ALK gene rearrangement in 7/594 cases (1%) by FISH and all anti-ALK antibodies correctly identified the seven ALK-positive cases (100% sensitivity), although the intensity of staining was weak in some cases. These data indicate that the use of antibodies with high sensitivity and avidity to ALK may provide an effective pre-screening technique to complement the more expensive and labor-intensive approach of ALK FISH testing.

Type Journal
ISBN 1530-0285 (Electronic) 0893-3952 (Linking)
Authors Selinger, C. I. ; Rogers, T. M. ; Russell, P. A. ; O'Toole, S. ; Yip, P.; Wright, G. M.; Wainer, Z. ; Horvath, L. G. ; Boyer, M. ; McCaughan, B; Kohonen-Corish, M. R. ; Fox, S. ; Cooper, W. A. ; Solomon, B.;
Garvan Authors Prof Sandra O'Toole
Publisher Name MODERN PATHOL
Published Date 2013-12-01 00:00:00
Published Volume 26
Published Issue 12
Published Pages 1545-53
URL http://www.ncbi.nlm.nih.gov/pubmed/23743928
Status Published In-print
OpenAccess Link https://publications.gimr.garvan.org.au/download.php?12077_12429/13_Selinger_ModPath_.pdf