title: 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.
authors.affiliation: Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
authors.forename: Christina I
authors.initials: CI
authors.lastname: Selinger
authors.forename: Toni-Maree
authors.initials: TM
authors.lastname: Rogers
authors.forename: Prudence A
authors.initials: PA
authors.lastname: Russell
authors.forename: Sandra
authors.initials: S
authors.lastname: O'Toole
authors.forename: Poyee
authors.initials: P
authors.lastname: Yip
authors.forename: Gavin M
authors.initials: GM
authors.lastname: Wright
authors.forename: Zoe
authors.initials: Z
authors.lastname: Wainer
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Horvath
authors.forename: Michael
authors.initials: M
authors.lastname: Boyer
authors.forename: Brian
authors.initials: B
authors.lastname: McCaughan
authors.forename: Maija Rj
authors.initials: MR
authors.lastname: Kohonen-Corish
authors.forename: Stephen
authors.initials: S
authors.lastname: Fox
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Cooper
authors.forename: Benjamin
authors.initials: B
authors.lastname: Solomon
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D046888:Tissue Array Analysis
chemical_list: C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases