Detection of t(2;5) in anaplastic large cell lymphoma: comparison of immunohistochemical studies, FISH, and RT-PCR in paraffin-embedded tissue

• Published in: The American journal of surgical pathology Vol. 23; no. 11; p. 1386
• Main Authors: Cataldo, K A, Jalal, S M, Law, M E, Ansell, S M, Inwards, D J, Fine, M, Arber, D A, Pulford, K A, Strickler, J G
• Format: Journal Article
• Language: English
• Published: United States 01.11.1999
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Anaplastic Lymphoma Kinase; Child; Child, Preschool; Female; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Lymphoma, Large B-Cell, Diffuse - genetics; Lymphoma, Large B-Cell, Diffuse - pathology; Male; Middle Aged; Paraffin Embedding; Protein-Tyrosine Kinases - biosynthesis; Receptor Protein-Tyrosine Kinases; Reverse Transcriptase Polymerase Chain Reaction; Translocation, Genetic
• ISSN: 0147-5185; 1532-0979
• DOI: 10.1097/00000478-199911000-00009

Anaplastic large cell lymphoma (ALCL) is associated with the t(2;5)(p23;q35) translocation involving the anaplastic lymphoma kinase gene (ALK) and the nucleophosmin gene (NPM), which result in expression of a novel fusion protein, NPM-ALK (p80). Clinicopathologic studies have shown that ALK expression in ALCL is associated with improved 5-year survival rates when compared with ALCL lacking ALK expression. This study used paraffin-embedded tissue to compare interphase fluorescence in situ hybridization (FISH) and reverse transcriptase-polymerase chain reaction (RT-PCR) for the detection of t(2;5) with immunohistochemical analysis for the detection of ALK protein expression in 27 patients with CD30-positive ALCLs. ALK protein expression was detected with ALK1 antibody in 14 of the 27 patients. The neoplastic cells in 13 of these 14 lymphomas reacted with the p80NPM/ALK antibody. FISH, using a two-color ALK DNA probe, correlated 100% with the immunohistochemical results: a translocation involving the ALK gene was detected in all 14 lymphomas that reacted with anti-ALK1. RT-PCR, performed on 21 lymphomas, detected NPM-ALK mRNA in five of the lymphomas, all of which reacted with anti-ALK1 and showed ALK gene rearrangement by FISH. Lymphomas showing ALK1 reactivity occurred in a younger patient population (median age, 19.5 years) and were associated with improved 5-year survival rates (84%), as compared with lymphomas lacking ALK1 reactivity (median age, 68.0 years; 5-year survival rate, 35%; p = 0.008). We conclude that immunohistochemical studies, using antibody ALK1. and FISH for ALK gene rearrangement are equally effective for identifying patients with ALCL who have a favorable clinical outcome.