Cancer-associated carbohydrate identification in Hodgkin's lymphoma by carbohydrate array profiling.
Tumor-associated carbohydrates have potential not only as diagnostic tools but also as specific therapeutic targets. Their identification, however, has been hampered by the lack of suitable technologies. We used carbohydrate array technology to compare serum antibody (IgG and IgM) levels against 37 different carbohydrates between classical Hodgkin's lymphoma (cHL) patients and age/sex-matched healthy controls. Serum IgM levels measured by ELISA against 2 of the 5 carbohydrates identified using this technique, L-alpha-arabinose (L-Araf) and alpha-N-acetylgalactosamine (GalNAc(alpha)), were higher (F values of 11.30 and 18.27, respectively) in a cohort of cHL patients (n = 16) than either diffuse large B-cell lymphoma patients (n = 18) or control sera (n = 12). Higher anti-L-Araf IgM levels in cHL patients were associated with cytosine arabinoside treatment (p < 0.05). The GalNAc(alpha) glycotope, Tn, was found to be heterogeneously expressed in the Reed-Sternberg cells of 9/20 (45%) cHL cases, but not in malignant cells of 25 cases of lymphocyte-predominant HL or another 21 hematological disorders (291 cases) examined immunohistochemically. Tn was expressed in 41/238 (17%) classical HL cases present on a tissue microarray. Expression was associated with CD79a and LMP1 expression and negatively with p27(KIP1) expression (p < 0.05). Kaplan-Meier survival analysis revealed a trend towards improved relapse-free survival with Tn expression although this was not statistically significant (p = 0.271). We suggest that this technique could provide a powerful tool for identifying novel carbohydrates in other cancers.
Lawrie
Charles H
CH
Nuffield Department of Clinical Laboratory Sciences, University of Oxford, John Radcliffe Hospital, UK. charles.lawrie@ndcls.ox.ac.uk
Marafioti
Teresa
T
Hatton
Christian S R
CS
Dirnhofer
Stephan
S
Roncador
Giovanna
G
Went
Philip
P
Tzankov
Alexandar
A
Pileri
Stefano A
SA
Pulford
Karen
K
Banham
Alison H
AH
D000116:Acetylgalactosamine / Q000097:blood; D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D001089:Arabinose / Q000097:blood; D051925:CD79 Antigens / Q000097:blood; D002241:Carbohydrates / Q000097:blood* / Q000276:immunology; D016022:Case-Control Studies; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000097:blood; D003598:Cytoskeletal Proteins; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006689:Hodgkin Disease / Q000097:blood*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000097:blood; D060588:LIM Domain Proteins; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis
D048868:Adaptor Proteins, Signal Transducing; D051925:CD79 Antigens; D002241:Carbohydrates; D003598:Cytoskeletal Proteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; C484380:PDLIM7 protein, human; D050760:Cyclin-Dependent Kinase Inhibitor p27; D001089:Arabinose; D000116:Acetylgalactosamine