title: Stratifying diffuse large B-cell lymphoma patients treated with chemoimmunotherapy: GCB/non-GCB by immunohistochemistry is still a robust and feasible marker.
abstract: Diffuse large B cell lymphoma (DLBCL) is a heterogeneous group of aggressive lymphomas that can be classified into three molecular subtypes by gene expression profiling (GEP): GCB, ABC and unclassified. Immunohistochemistry-based cell of origin (COO) classification, as a surrogate for GEP, using three available immunohistochemical algorithms was evaluated in TMA-arranged tissue samples from 297 patients with de novo DLBCL treated by chemoimmunotherapy (R-CHOP and R-CHOP-like regimens). Additionally, the prognostic impacts of MYC, BCL2, IRF4 and BCL6 abnormalities detected by FISH, the relationship between the immunohistochemical COO classification and the immunohistochemical expression of MYC, BCL2 and pSTAT3 proteins and clinical data were evaluated. In our series, non-GCB DLBCL patients had significantly worse progression-free survival (PFS) and overall survival (OS), as calculated using the Choi, Visco-Young and Hans algorithms, indicating that any of these algorithms would be appropriate for identifying patients who require alternative therapies to R-CHOP. Whilst MYC abnormalities had no impact on clinical outcome in the non-GCB subtype, those patients with isolated MYC rearrangements and a GCB-DLBCL phenotype had worse PFS and therefore might benefit from novel treatment approaches.
authors.affiliation: Departments of Haematology and Pathology, Hospital Marques de Valdecilla, and IDIVAL, Santander, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Batlle-López
authors.affiliation: Departments of Haematology and Pathology, Hospital Marques de Valdecilla, and IDIVAL, Santander, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: González de Villambrosía
authors.affiliation: Departments of Haematology and Pathology, Hospital Marques de Valdecilla, and IDIVAL, Santander, Spain.
authors.forename: Mazorra
authors.initials: M
authors.lastname: Francisco
authors.affiliation: Departments of Haematology and Pathology, Hospital Marques de Valdecilla, and IDIVAL, Santander, Spain.
authors.forename: Sefora
authors.initials: S
authors.lastname: Malatxeberria
authors.affiliation: Biobanco del Sistema Sanitario Público de Andalucía, Granada, Spain.
authors.forename: Anabel
authors.initials: A
authors.lastname: Sáez
authors.affiliation: MD Anderson Cancer Center, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Montalban
authors.affiliation: Biotechnology Programme, Histology and Immunohistochemistry Core Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
authors.forename: Lydia
authors.initials: L
authors.lastname: Sánchez
authors.affiliation: Pathology, MD Anderson Cancer Center, Madrid, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Garcia
authors.affiliation: Department of Haematology, Hospital de Bellvitge (ICOIRO), Barcelona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: González-Barca
authors.affiliation: Departments of Pathology and Haematology, Hospital Vall d'Hebron, Barcelona, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: López-Hernández
authors.affiliation: Departments of Pathology and Haematology, Hospital Vall d'Hebron, Barcelona, Spain.
authors.forename: M C
authors.initials: MC
authors.lastname: Ruiz-Marcellan
authors.affiliation: Hospital Virgen de la Salud, Toledo, Spain.
authors.forename: Manuela
authors.initials: M
authors.lastname: Mollejo
authors.affiliation: Hematology, Hospital 12 de Octubre, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Grande
authors.affiliation: Department of Hematology-Oncology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
authors.forename: Kristy L
authors.initials: KL
authors.lastname: Richards
authors.affiliation: Department of Clinical Pathology, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Hsi
authors.affiliation: University Hospital, Basel, Switzerland.
authors.forename: Alexandar
authors.initials: A
authors.lastname: Tzankov
authors.affiliation: Department of Hematology, San Bortolo Hospital, Vicenza, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Visco
authors.affiliation: Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Zijun Y
authors.initials: ZY
authors.lastname: Xu-Monette
authors.affiliation: Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Cao
authors.affiliation: Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Ken H
authors.initials: KH
authors.lastname: Young
authors.affiliation: Departments of Haematology and Pathology, Hospital Marques de Valdecilla, and IDIVAL, Santander, Spain.
authors.forename: Miguel Ángel
authors.initials: MÁ
authors.lastname: Piris
authors.affiliation: Departments of Haematology and Pathology, Hospital Marques de Valdecilla, and IDIVAL, Santander, Spain.
authors.forename: Eulogio
authors.initials: E
authors.lastname: Conde
authors.affiliation: Departments of Haematology and Pathology, Hospital Marques de Valdecilla, and IDIVAL, Santander, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Montes-Moreno
mesh_terms: D000465:Algorithms; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D006801:Humans; D007150:Immunohistochemistry; D016403:Lymphoma, Large B-Cell, Diffuse / Q000145:classification* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D012189:Retrospective Studies; D000069283:Rituximab / Q000008:administration & dosage; D016019:Survival Analysis; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; C571759:R-CHOP protocol; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone
keywords: BCL2; BCL6; DLBCL; MYC; non-GCB and GCB