BACKGROUND: Gene expression profiling of diffuse large B cell lymphoma (DLBCL) revealed three disease types: germinal centre B cell-like (GC), activated B cell-like (ABC), and a "third" type. Expression of CD44 variant isoforms (CD44v) is associated with an unfavourable clinical outcome in DLBCL, but previous studies did not consider the clinicopathological heterogeneity of this disease. AIMS: To analyse the expression and prognostic significance of CD44 in DLBCL types. METHODS: A tissue microarray (TMA) comprising 90 DLBCLs was constructed. CD10, CD20, bcl-2, bcl-6, CD44 standard isoform (CD44s), and CD44v4, CD44v6, and CD44v9 were analysed immunohistochemically and correlated with clinical follow up. RESULTS: TMA expression of CD10, CD20, bcl-2, and bcl-6 showed 100% concordance with results from conventional sections in 60 cases. Samples were segregated into 22 GC (bcl-6+/CD10+/bcl-2-), 25 ABC (bcl-6-/CD10-/bcl-2+), and 35 unclassifiable DLBCLs. Overall survival (OS) at 30 months was 89%, 44%, and 58% in GC, ABC, and unclassified types, respectively. CD44v6 was coexpressed with bcl-2, appeared predominantly on bcl-6 negative cases, and correlated with disease stage. Cases negative for CD44s could be separated into CD44v6 negative (OS, 82% at 70 months) and CD44v6 positive (OS, 58%). CONCLUSIONS: TMA technology is useful for immunophenotyping and clinicopathological analysis of large lymphoma populations. The GC phenotype of DLBCL is of independent prognostic significance for OS. Expression of CD44v6 correlates with disease stage, and might contribute to lymphoma dissemination. CD44v6 is expressed predominantly in ABC DLBCL, and in CD44 negative cases is associated with worse OS.
BACKGROUND: Gene expression profiling of diffuse large B cell lymphoma (DLBCL) revealed three disease types: germinal centre B cell-like (GC), activated B cell-like (ABC), and a "third" type. Expression of CD44 variant isoforms (CD44v) is associated with an unfavourable clinical outcome in DLBCL, but previous studies did not consider the clinicopathological heterogeneity of this disease. AIMS: To analyse the expression and prognostic significance of CD44 in DLBCL types. METHODS: A tissue microarray (TMA) comprising 90 DLBCLs was constructed. CD10, CD20, bcl-2, bcl-6, CD44 standard isoform (CD44s), and CD44v4, CD44v6, and CD44v9 were analysed immunohistochemically and correlated with clinical follow up. RESULTS:TMA expression of CD10, CD20, bcl-2, and bcl-6 showed 100% concordance with results from conventional sections in 60 cases. Samples were segregated into 22 GC (bcl-6+/CD10+/bcl-2-), 25 ABC (bcl-6-/CD10-/bcl-2+), and 35 unclassifiable DLBCLs. Overall survival (OS) at 30 months was 89%, 44%, and 58% in GC, ABC, and unclassified types, respectively. CD44v6 was coexpressed with bcl-2, appeared predominantly on bcl-6 negative cases, and correlated with disease stage. Cases negative for CD44s could be separated into CD44v6 negative (OS, 82% at 70 months) and CD44v6 positive (OS, 58%). CONCLUSIONS:TMA technology is useful for immunophenotyping and clinicopathological analysis of large lymphoma populations. The GC phenotype of DLBCL is of independent prognostic significance for OS. Expression of CD44v6 correlates with disease stage, and might contribute to lymphoma dissemination. CD44v6 is expressed predominantly in ABC DLBCL, and in CD44 negative cases is associated with worse OS.
Authors: Margaret A Shipp; Ken N Ross; Pablo Tamayo; Andrew P Weng; Jeffery L Kutok; Ricardo C T Aguiar; Michelle Gaasenbeek; Michael Angelo; Michael Reich; Geraldine S Pinkus; Tane S Ray; Margaret A Koval; Kim W Last; Andrew Norton; T Andrew Lister; Jill Mesirov; Donna S Neuberg; Eric S Lander; Jon C Aster; Todd R Golub Journal: Nat Med Date: 2002-01 Impact factor: 53.440
Authors: S A Pileri; S Dirnhofer; Ph Went; S Ascani; E Sabattini; T Marafioti; A Tzankov; L Leoncini; B Falini; P L Zinzani Journal: Histopathology Date: 2002-12 Impact factor: 5.087
Authors: E Horst; C J Meijer; T Radaskiewicz; J J van Dongen; R Pieters; C G Figdor; A Hooftman; S T Pals Journal: Leukemia Date: 1990-05 Impact factor: 11.528
Authors: Andreas Rosenwald; George Wright; Wing C Chan; Joseph M Connors; Elias Campo; Richard I Fisher; Randy D Gascoyne; H Konrad Muller-Hermelink; Erlend B Smeland; Jena M Giltnane; Elaine M Hurt; Hong Zhao; Lauren Averett; Liming Yang; Wyndham H Wilson; Elaine S Jaffe; Richard Simon; Richard D Klausner; John Powell; Patricia L Duffey; Dan L Longo; Timothy C Greiner; Dennis D Weisenburger; Warren G Sanger; Bhavana J Dave; James C Lynch; Julie Vose; James O Armitage; Emilio Montserrat; Armando López-Guillermo; Thomas M Grogan; Thomas P Miller; Michel LeBlanc; German Ott; Stein Kvaloy; Jan Delabie; Harald Holte; Peter Krajci; Trond Stokke; Louis M Staudt Journal: N Engl J Med Date: 2002-06-20 Impact factor: 91.245
Authors: Cyrus V Hedvat; Abhijith Hegde; Raju S k Chaganti; Beiyun Chen; Jing Qin; Daniel A Filippa; Stephen D Nimer; Julie Teruya-Feldstein Journal: Hum Pathol Date: 2002-10 Impact factor: 3.466
Authors: Ellen C Obermann; Philip Went; Alexandar Tzankov; Stefano A Pileri; Ferdinand Hofstaedter; Joerg Marienhagen; Robert Stoehr; Stephan Dirnhofer Journal: J Clin Pathol Date: 2006-09-01 Impact factor: 3.411
Authors: Sonja Eberth; Björn Schneider; Andreas Rosenwald; Elena M Hartmann; Julia Romani; Margarete Zaborski; Reiner Siebert; Hans G Drexler; Hilmar Quentmeier Journal: BMC Cancer Date: 2010-09-29 Impact factor: 4.430
Authors: Matilde Cacciatore; Carla Guarnotta; Marco Calvaruso; Sabina Sangaletti; Ada Maria Florena; Vito Franco; Mario Paolo Colombo; Claudio Tripodo Journal: Adv Hematol Date: 2012-02-19