TY - JOUR
T1 - MYC cytogenetic status correlates with expression and has prognostic significance in patients with MYC/BCL2 protein double-positive diffuse large B-cell lymphoma
AU - Wang, Xuan Julia
AU - Medeiros, L. Jeffrey
AU - Lin, Pei
AU - Yin, C. Cameron
AU - Hu, Shimin
AU - Thompson, Mary Ann
AU - Li, Shaoying
N1 - Publisher Copyright:
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2015
Y1 - 2015
N2 - MYC/BCL2 double-hit lymphoma (DHL), defined by conventional cytogenetic or fluorescence in situ hybridization (FISH) analysis, and MYC/BCL2 double-positive lymphoma (DPL), defined by immunohistochemistry, are associated with a poor prognosis. However, DHL and DPL are not concordant, and it is unclear whether MYC and BCL2 aberrations have prognostic impact in DPL patients. In a cohort of 135 patients diagnosed with large B-cell lymphoma between 2010 and 2014 in whom MYC/8q24 and BCL2/t(14;18)(q32;q21) statuses were assessed by FISH at diagnosis, we evaluated MYC and BCL2 expression by immunohistochemistry. A total of 54 (40%) cases were positive for MYC and BCL2 supporting DPL. Among them, 19 (35%) had MYC rearrangement including 11 DHLs, 12 (22%) had multiple copies of MYC, 19 had no MYC abnormalities, and in 4 cases FISH analysis failed. BCL2 abnormalities were present in 28/54 (52%) cases (20 rearranged and 8 multiple copies). MYC rearrangement correlated with a significantly worse overall survival in DPL (P0.05), whereas BCL2 genetic status did not correlate with survival (P0.05). MYC and BCL2 expression by immunohistochemistry correlates with gene status by FISH; however, immunohistochemistry is neither specific nor adequately sensitive to be used as a surrogate for MYC and BCL2 gene status using any cutoff level. In conclusion, MYC rearrangement identifies a subset of patients with DPL who have a significantly worse prognosis. Although immunohistochemical assessment for MYC and BCL2 may be a helpful initial screen to identify higher-risk patients, FISH analysis for MYC remains important for further risk stratification in patients with DPL.
AB - MYC/BCL2 double-hit lymphoma (DHL), defined by conventional cytogenetic or fluorescence in situ hybridization (FISH) analysis, and MYC/BCL2 double-positive lymphoma (DPL), defined by immunohistochemistry, are associated with a poor prognosis. However, DHL and DPL are not concordant, and it is unclear whether MYC and BCL2 aberrations have prognostic impact in DPL patients. In a cohort of 135 patients diagnosed with large B-cell lymphoma between 2010 and 2014 in whom MYC/8q24 and BCL2/t(14;18)(q32;q21) statuses were assessed by FISH at diagnosis, we evaluated MYC and BCL2 expression by immunohistochemistry. A total of 54 (40%) cases were positive for MYC and BCL2 supporting DPL. Among them, 19 (35%) had MYC rearrangement including 11 DHLs, 12 (22%) had multiple copies of MYC, 19 had no MYC abnormalities, and in 4 cases FISH analysis failed. BCL2 abnormalities were present in 28/54 (52%) cases (20 rearranged and 8 multiple copies). MYC rearrangement correlated with a significantly worse overall survival in DPL (P0.05), whereas BCL2 genetic status did not correlate with survival (P0.05). MYC and BCL2 expression by immunohistochemistry correlates with gene status by FISH; however, immunohistochemistry is neither specific nor adequately sensitive to be used as a surrogate for MYC and BCL2 gene status using any cutoff level. In conclusion, MYC rearrangement identifies a subset of patients with DPL who have a significantly worse prognosis. Although immunohistochemical assessment for MYC and BCL2 may be a helpful initial screen to identify higher-risk patients, FISH analysis for MYC remains important for further risk stratification in patients with DPL.
KW - Double-hit lymphoma
KW - MYC immunohistochemistry
KW - MYC rearrangement
KW - MYC/BCL2 double-positive lymphoma
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U2 - 10.1097/PAS.0000000000000433
DO - 10.1097/PAS.0000000000000433
M3 - Article
C2 - 25828389
AN - SCOPUS:84942768754
SN - 0147-5185
VL - 39
SP - 1250
EP - 1258
JO - American Journal of Surgical Pathology
JF - American Journal of Surgical Pathology
IS - 9
ER -