title: Expression of CD8 is associated with non-common type morphology and outcome in pediatric anaplastic lymphoma kinase-positive anaplastic large cell lymphoma.
abstract: Anaplastic lymphoma kinase-positive anaplastic large T-cell lymphoma is characterized by morphological variability. Morphological variants (non-common subtype) are associated with a poor outcome. They display abundant reactive bystander cells admixed with the lymphoma cells. So far, the difficulty in distinguishing lymphoma cells from bystander cells by visual inspection has prevented detailed and reliable immunophenotypic analysis using conventional immunohistochemistry. To overcome these limitations, we analyzed 124 cases of pediatric anaplastic lymphoma kinase-positive anaplastic large cell lymphoma treated within clinical trials using immunofluorescence multi-staining and digital image analysis combining antibodies against anaplastic lymphoma kinase to specifically identify lymphoma cells with antibodies against CD30, CD3, CD5, CD8, Ki67 and phosphorylated STAT3. Non-common type anaplastic lymphoma kinase-positive anaplastic large cell lymphomas express CD8 more frequently than common type anaplastic lymphoma kinase-positive anaplastic large cell lymphomas (35.4% and 5.6%, respectively; P=0.0002). CD8 expression was associated with a poorer outcome. Importantly, in a multivariate analysis including clinical risk factors, histological subtype and CD8 expression, CD8-positivity proved to be an independent prognostic predictor of worse outcome (hazard ratio for survival 3.38, P=0.042).
authors.affiliation: wklapper@path.uni-kiel.de.
authors.forename: Dmitriy
authors.initials: D
authors.lastname: Abramov
authors.forename: Ilske
authors.initials: I
authors.lastname: Oschlies
authors.forename: Martin
authors.initials: M
authors.lastname: Zimmermann
authors.forename: Dmitriy
authors.initials: D
authors.lastname: Konovalov
authors.forename: Christine
authors.initials: C
authors.lastname: Damm-Welk
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Wössmann
authors.forename: Wolfram
authors.initials: W
authors.lastname: Klapper
mesh_terms: D000293:Adolescent; D000077548:Anaplastic Lymphoma Kinase; D016827:CD8 Antigens / Q000096:biosynthesis*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D017728:Lymphoma, Large-Cell, Anaplastic / Q000175:diagnosis* / Q000201:enzymology* / Q000628:therapy; D008297:Male; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis*; D016896:Treatment Outcome
chemical_list: D016827:CD8 Antigens; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases