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

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 pro tein, NPM-ALK (p80). Clinicopathologic studies have shown chat ALK expressi on 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 expre ssion in 27 patients with CD30-positive ALCLs. ALK protein expression was d etected with ALK1 antibody in 14 of the 27 patients. The neoplastic cells i n 13 of these 14 lymphomas reacted with the p80(NPM/ALK) antibody. FISH, us ing a two-color ALK DNA probe, correlated 100% with the immunohistochemical results: a translocation involving the ALK gene was detected in all 14 lym phomas that: reacted with anti-ALK1. RT-PCR, performed on 21 lymphomas, det ected 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 rea ctivity occurred in a younger patient population (median age, 19.5 years) a nd were associated with improved 5-year survival rates (84%), as compared w ith lymphomas lacking ALK1 reactivity (median age, 68.0 years; 5-year survi val rate, 35%; p = 0.008). We conclude that immunohistochemical studies, us ing antibody ALK1, and FISH for ALK gene rearrangement are equally effectiv e for identifying patients with ALCL who have a favorable clinical outcome.