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 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.
Cataldo
K A
KA
Department of Laboratory Medicine and Pathology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA.
Jalal
S M
SM
Law
M E
ME
Ansell
S M
SM
Inwards
D J
DJ
Fine
M
M
Arber
D A
DA
Pulford
K A
KA
Strickler
J G
JG
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D016612:Paraffin Embedding; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis*; D020794:Receptor Protein-Tyrosine Kinases; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic
C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases