Expression of Myc, but not pSTAT3, is an adverse prognostic factor for diffuse large B-cell lymphoma treated with epratuzumab/R-CHOP

WOS: 000313111300022
PubMed ID: 23018644
STAT3 regulates cell growth by upregulating downstream targets, such as Myc. The frequency of phosphorylated STAT3 (pSTAT3) and Myc expression and their prognostic relevance is unknown within diffuse large B-cell lymphoma (DLBCL) germinal center B-cell (GCB) and non-GCB subtypes. pSTAT3 and Myc were studied by immunohistochemistry (IHC) on tumors from 40 DLBCL patients uniformly treated on a clinical trial of epratuzumab/rituximab-CHOP. A total of 35% of cases were pSTAT3-positive, and pSTAT3 positivity was more frequent in the non-GCB (P = .06) type but did not correlate with event-free survival (EFS). Myc expression was observed in 50% of cases and was more frequent in non-GCB type (P = .07). Myc-positive cases had inferior EFS in all patients, including the GCB and pSTAT3-positive cases, were more likely to express Myc (P = .06). Myc translocations involving the major breakpoint regions were found in 10% (3 of 29) of cases, and all 3 cases were GCB and had an inferior EFS (P = .09). pSTAT3, but not Myc expression, was correlated with elevated pretreatment serum cytokines, such as IL-10 (P = .05), G-CSF (P = .03), and TNF-alpha (P = .04). pSTAT3 IHC in DLBCL tumors has the potential to identify patients for STAT3 pathway-directed therapy; Myc IHC is a potential marker for inferior EFS in GCB patients. (Blood. 2012;120(22):4400-4406)
University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence [P50 CA097274]; Goodwin Foundation; North Central Cancer Treatment Group [CA25224, CA114740]; Predolin Foundation; [R01-CA127433]
This work was supported in part by the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence (Career Development Award P50 CA097274; M.G.), Goodwin Foundation Pilot award (M.G.), the North Central Cancer Treatment Group (CA25224; and Biospecimen Resource Grant CA114740), and the Predolin Foundation Award. This work is supported in part by R01-CA127433 to T.E.W.