title: Expression of Myc, but not pSTAT3, is an adverse prognostic factor for diffuse large B-cell lymphoma treated with epratuzumab/R-CHOP.
abstract: STAT3 regulates cell growth by up-regulating 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-α (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.
authors.affiliation: Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA. gupta.mamta@mayo.edu
authors.forename: Mamta
authors.initials: M
authors.lastname: Gupta
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Maurer
authors.forename: Linda E
authors.initials: LE
authors.lastname: Wellik
authors.forename: Mark E
authors.initials: ME
authors.lastname: Law
authors.forename: Jing Jing
authors.initials: JJ
authors.lastname: Han
authors.forename: Nazan
authors.initials: N
authors.lastname: Ozsan
authors.forename: Ivana N
authors.initials: IN
authors.lastname: Micallef
authors.forename: Ahmet
authors.initials: A
authors.lastname: Dogan
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Witzig
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D054316:Biomarkers, Pharmacological / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism / Q000502:physiology; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism; D008875:Middle Aged; D010766:Phosphorylation; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D011494:Protein Kinases / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism / Q000502:physiology*; D000069283:Rituximab; D050796:STAT3 Transcription Factor / Q000378:metabolism / Q000502:physiology*; D016896:Treatment Outcome; D054928:Validation Studies as Topic; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D054316:Biomarkers, Pharmacological; D014408:Biomarkers, Tumor; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; C571759:R-CHOP protocol; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C448700:epratuzumab; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011494:Protein Kinases; D011241:Prednisone