title: The stromal cell marker SPARC predicts for survival in patients with diffuse large B-cell lymphoma treated with rituximab.
abstract: The cellular composition of the tumor microenvironment may affect survival in diffuse large B-cell lymphoma (DLBCL). We performed immunostains for 2 stromal cell markers, CD68 and SPARC (secreted protein, acidic and rich in cysteine), in 262 patients with DLBCL treated with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like therapies. Patients with any SPARC+ cells in the microenvironment had a significantly longer overall survival, and patients with high SPARC positivity in the microenvironment also had a significantly longer event-free survival. Survival differences were mainly due to the prognostic effect of SPARC+ cells in activated B-cell (ABC)-type DLBCL, with no effect found in the germinal center B-cell-type DLBCL. Of clinical features examined, only the number of extranodal sites was significantly associated with SPARC expression. Multivariate analysis revealed that SPARC expression predicted patient survival independent of the International Prognostic Index or tumor cell of origin. SPARC expression in the microenvironment of DLBCL can be used for prognostic purposes, determining a subgroup of patients with ABC DLBCL who have significantly longer survival. More aggressive chemotherapy protocols should be considered for patients with ABC DLBCL without SPARC+ stromal cells. CD68 expression by cells in the microenvironment did not predict survival.
authors.affiliation: Dept of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, 68198, USA.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Meyer
authors.forename: Kai
authors.initials: K
authors.lastname: Fu
authors.forename: Timothy
authors.initials: T
authors.lastname: Greiner
authors.forename: Lynette
authors.initials: L
authors.lastname: Smith
authors.forename: Jan
authors.initials: J
authors.lastname: Delabie
authors.forename: Randy
authors.initials: R
authors.lastname: Gascoyne
authors.forename: German
authors.initials: G
authors.lastname: Ott
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
authors.forename: Rita
authors.initials: R
authors.lastname: Braziel
authors.forename: Elias
authors.initials: E
authors.lastname: Campo
authors.forename: Julie
authors.initials: J
authors.lastname: Vose
authors.forename: Georg
authors.initials: G
authors.lastname: Lenz
authors.forename: Louis
authors.initials: L
authors.lastname: Staudt
authors.forename: Wing
authors.initials: W
authors.lastname: Chan
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Weisenburger
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D015676:Osteonectin / Q000378:metabolism*; D011241:Prednisone / Q000008:administration & dosage / Q000627:therapeutic use; D011379:Prognosis; D000069283:Rituximab; D015996:Survival Rate; D014750:Vincristine / Q000008:administration & dosage / Q000627:therapeutic use; D000097382:CD68 Molecule
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D003520:Cyclophosphamide; D004317:Doxorubicin; D015676:Osteonectin; D011241:Prednisone; D000069283:Rituximab; D014750:Vincristine; C067980:CD68 antigen, human; D000097382:CD68 Molecule