Journal article
Prognostic Significance and Phenotypic Manifestations of MYC/BCL2 Protein Expression in Diffuse Large B-Cell Lymphoma (DLBCL) with Extranodal Organ Involvement: A Report of the International DLBCL Rituximab-CHOP Consortium Program Study
-
Madadi, Anusha
Gundersen Lutheran Health System, Center for Cancer and Blood Disorders, La Crosse, WI, USA,
-
Raghavendra, Meghana
Center for cancer and blood disorders, Gundersen Lutheran Medical Center, La Crosse, WI, USA,
-
Hu, Shimin
Hematopathology, M.D. Anderson Cancer Center, Houston, TX, USA,
-
Xu-Monette, Zijun Y.
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA,
-
Visco, Carlo
Department of Hematology, San Bortolo Hospital, Vicenza, Italy,
-
Tzankov, Alexander
Department of Pathology, University Hospital of Basel, Basel, Switzerland,
-
Montes-Moreno, Santiago
Department of Pathology, Hospital Universitario Marques de Valdecilla, Santander, Spain,
-
Dybkaer, Karen
Department of Haematology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark,
-
Chiu, April
Hematologic pathology, 7Memorial Sloan-Kettering Cancer Center, New York, NY, USA,
-
Orazi, Attilio
Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY, USA,
-
Zu, Youli
Department of Pathology, The Methodist Hospital, Houston, TX, USA,
-
Bhagat, Govind
Department of Pathology & Cell Biology, Columbia University Medical Center, New York, NY, USA,
-
Dunphy, Cherie H.
Department of Pathology, University of North Carolina, Chapel Hill, NC, USA,
-
Hsi, Eric D.
Department of Clinical Pathology, Cleveland Clinic, Cleveland, OH, USA,
-
Zhao, Frank X.
Department of Pathology, Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA,
-
Choi, William W. L.
Department of Pathology, University of Hong Kong, Hong Kong, China,
-
Zhao, Xiaoying
Department of Medicine-Hematology/Oncology, Zhejiang University School of Medicine, Second University Hospital, Hangzhou, China,
-
Van Krieken, Joannes H.J.M.
Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands,
-
Huh, Jooryung
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea,
-
Huang, Qin
Department of Pathology, City of Hope National Cancer Center, Duarte, CA, USA,
-
Ai, Wei
Hematology/Oncology, University of California San Francisco School of Medicine, San Francisco, CA,
-
Ponzoni, Maurilio
Pathology Unit and Unit of Lymphoid Malignancies, San Raffaele Scientific Institute, Milan, Italy,
-
Ferreri, Andrés J.M.
Unit of Lymphoid Malignancies, Department of Onco-Hematology, San Raffaele Scientific Institute, Milano, Italy,
-
Zhou, Fan
Department of Pathology, Southwest Washington Medical Center, Vancouver, WA, USA,
-
Winter, Jane N.
Northwestern University Feinberg School of Medicine, Chicago, IL, USA,
-
Piris, Miguel
Departments of Pathology and Haematology, Hospital Marques de Valdecilla, Santander, Spain,
-
Møller, Michael B.
Department of Pathology, Odense University Hospital, Odense, Denmark,
-
Medeiros, L. Jeffrey
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA,
-
Go, Ronald S.
Center for Cancer and Blood Disorders, Gundersen Lutheran Health System, La Crosse, WI, USA
-
Young, Ken H.
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA,
Show more…
Published in:
- Blood. - American Society of Hematology. - 2012, vol. 120, no. 21, p. 544-544
English
Abstract
Abstract 544
Background:
In DLBCL, multiple extranodal sites of involvement and MYC/BCL2 translocations (double hit lymphoma) are associated with a poor clinical outcome. The association between the pattern of extranodal involvement and MYC and BCL2 protein expression, as well as the prognostic significance of expression, are unknown.
Methods:
We analyzed the clinical data of 487 DLBCL patients treated with R-CHOP. Immunohistochemical (IHC) studies were performed on paraffin-embedded tissue samples for MYC and BCL2. A double-hit score (DHS) of 0, 1, or 2 was assigned to all patients based on protein expression of MYC and BCL2. Those with both MYC and BCL2 expression were DHS 2, with MYC or BCL2 was DHS 1, and neither was DHS 0. Cell-of-origin classification was achieved by combining gene expression profiling (GEP) and IHC data with GEP as the gold standard. Patient characteristics were compared using Fisher's exact test. Survival analyses were performed using Kaplan-Meier curves and compared using log-rank test. The Cox proportional regression model was used for multivariate analysis.
Results:
Approximately half of the patients (n = 251; 51.5%) had at least 1 extranodal site of involvement. In this group, the clinical features were: median age of 63 years (range, 12–88), male (58.6%), stage III/IV (63.2%), elevated serum LDH (66.8%), and International Prognostic Index (IPI) of 3–5 (48.5%). IHC features were: non-germinal center B-cell like (non-GCB) (53%), MYC+ (64.9%), BCL2+ (49.8%), MYC-/BCL2- (DHS 0; 20.3%), MYC+/BCL2- or MYC-/BCL2+ (DHS 1; 44.6%) and MYC+/BCL2+ (DHS 2; 35.1%).
The common extranodal sites of involvement were genitourinary tract (18.3%), gastrointestinal tract (15.1%), sinonasal (14.3%), bones (13.9 %), lung (11.6 %), skin/soft tissues (9.9%), liver (9.1%), and bone marrow (8.4%). MYC+ was associated with bone marrow (odds ratio [OR]: 5.67; P = 0.009) and skin (OR: 3.11; P = 0.045) involvement, BCL2+ with sinonasal (OR: 2.26; P = 0.032) involvement, and MYC+/BCL2+ with skin/soft tissue (OR: 2.38; P = 0.049) and lung (OR: 2.37; P = 0.04) involvement. Non-GCB subtype was associated with genitourinary tract (OR: 1.47; P = 0.005) and bone marrow involvement (OR: 1.5; P = 0.038).
The DHS 2 subgroup was significantly associated with lower complete response rate (62.5% vs 76.1%; P = 0.023), shorter progression-free-survival (PFS) (median 23.1 months vs 80.7 months; P < 0.001), and shorter overall survival (OS) (median 25.0 months vs 94.5 months; P < 0.001) compared with the DHS 0–1 subgroups. Using multivariate analysis, DHS 2 remained significantly associated with a worse outcome.
Conclusions:
In DLBCL with extranodal disease, MYC and BCL2 protein expressions and cell-of-origin are associated with distinct patterns of organ involvement. Patients with DLBCL expressing both MYC and BCL2 (score DHS 2; double hit biology) have a poor outcome independent of IPI and cell-of-origin.
Disclosures:
No relevant conflicts of interest to declare.
-
Language
-
-
Open access status
-
closed
-
Identifiers
-
-
Persistent URL
-
https://sonar.ch/global/documents/2895
Statistics
Document views: 17
File downloads: