Coexpression of CD44 variant isoforms and receptor for hyaluronic acid-mediated motility (RHAMM, CD168) is an International Prognostic Index and C-MYC gene status-independent predictor of poor outcome in diffuse large B-cell lymphomas.
OBJECTIVE
Expression of CD44 variant (v) isoforms substantiates poor prognosis in patients with hematological malignancies. We have previously shown that CD44v6 expression in diffuse large B-cell lymphoma (DLBCL) correlates with advanced disease stage and is predominantly detected in non-germinal center B-cell-like DLBCL subtypes. With the growing number of associated molecules found to form functional complexes with CD44, we analyzed a larger cohort of cyclophosphamide, doxorubicin, vincristine, prednisone, and equivalently treated DLBCL patients to define the prognostic role of such CD44-associated molecules.


METHODS
Two-hundred and ninety formalin-fixed, paraffin-embedded primary DLBCL tissue samples were analyzed in tissue microarrays. To obtain potential biologically meaningful associations, optimal cutoff values were established by receiver operating characteristic curves. The prognostic significance of every possible multimarker phenotype was also addressed.


RESULTS
We showed that coexpression of any of the CD44v with the receptor for hyaluronic acid-mediated motility (RHAMM, CD168) identifies a subgroup of DLBCL patients with a very poor prognosis, independent of the International Prognostic Index. These patients did not show C-MYC translocations or amplifications. CD44v-RHAMM coexpression was most prevalent in non-germinal center DLBCL cases and usually coincided with expression of osteopontin.


CONCLUSIONS
Evaluation of CD44v-RHAMM coexpression may improve the accuracy of DLBCL prognosis and identify a subgroup of patients who will benefit from therapeutic alternatives to cyclophosphamide, doxorubicin, vincristine, and prednisone.
Institute of Pathology, Basel, Switzerland.
Sabine
S
Nagel
Petra
P
Hirschmann
Stephan
S
Dirnhofer
Ursula
U
Günthert
Alexandar
A
Tzankov
D000368:Aged; D000369:Aged, 80 and over; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D016259:Genes, myc; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics*; D007150:Immunohistochemistry; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D046888:Tissue Array Analysis
D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; C098946:hyaluronan-mediated motility receptor