Stratifying diffuse large B-cell lymphoma patients treated with chemoimmunotherapy: GCB/non-GCB by immunohistochemistry is still a robust and feasible marker
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Ana Batlle-López1, Sonia González de Villambrosía1, Mazorra Francisco1, Sefora Malatxeberria1, Anabel Sáez2, Carlos Montalban3, Lydia Sánchez4, Juan F. Garcia5, Eva González-Barca6, Andrés López-Hernández7, MC Ruiz-Marcellan7, Manuela Mollejo8, Carlos Grande9, Kristy L. Richards10, Eric D. Hsi11, Alexandar Tzankov12, Carlo Visco13, Zijun Y. Xu-Monette14, Xin Cao14, Ken H. Young14, Miguel Ángel Piris1, Eulogio Conde1, Santiago Montes-Moreno1
1Departments of Haematology and Pathology, Hospital Marques de Valdecilla, and IDIVAL, Santander, Spain
2Biobanco del Sistema Sanitario Público de Andalucía, Granada, Spain
3MD Anderson Cancer Center, Madrid, Spain
4Biotechnology Programme, Histology and Immunohistochemistry Core Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
5Pathology, MD Anderson Cancer Center, Madrid, Spain
6Department of Haematology, Hospital de Bellvitge (ICOIRO), Barcelona, Spain
7Departments of Pathology and Haematology, Hospital Vall d’Hebron, Barcelona, Spain
8Hospital Virgen de la Salud, Toledo, Spain
9Hematology, Hospital 12 de Octubre, Madrid, Spain
10Department of Hematology-Oncology, University of North Carolina School of Medicine, Chapel Hill, NC, USA
11Department of Clinical Pathology, Cleveland Clinic, Cleveland, OH, USA
12University Hospital, Basel, Switzerland
13Department of Hematology, San Bortolo Hospital, Vicenza, Italy
14Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
Ana Batlle López, email: email@example.com
Keywords: MYC, BCL2, BCL6, non-GCB and GCB, DLBCL
Received: August 23, 2015 Accepted: February 02, 2016 Published: February 19, 2016
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.
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