[1595] Amplification and Gain of Extra Copies of MYC and BCL-2 Are Common Genetic Abnormalities in Diffuse Large B-Cell Lymphoma (DLBCL)

Josette William Ragheb, Zhang Yanming, LoAnn Peterson, Juehua Gao, Yi-hua Chen. Northwestern University Feinberg School of Medicine, Chicago, IL

Background: C-MYC and BCL-2 genes are activated through several mechanisms including chromosomal translocation and gene amplification. Recently, MYC or MYC /BCL-2 rearrangement has been found in a subset of DLBCL and is associated with poor prognosis. However, the data on MYC protein expression and MYC or BCL-2 gene alterations other than translocation in DLBCL is very limited.
Design: c-MYC and BCL-2 expression was assessed by immunohistochemistry (IHC) in 100 cases of DLBCLs. IHC for CD10, BCL-6, MUM-1, and Ki-67 was also performed in the same cohort of patients. FISH for MYC using break apart probe and FISH for BCl-2 using dual color probe for t(14;18) were performed in 33 cases. The results of IHC for c-MYC and BCL-2 were correlated with FISH analysis, Han's classification and the proliferation index.
Results: Ninety of 100 (90%) DLBCLs showed positive nuclear staining for c-MYC in 10 to 90% of cells. FISH analysis in 33 cases showed 5 (15%) were positive for MYC translocation and 20 (61%) had extra copies/amplification of MYC. The MYC gene abnormalities were significantly correlated with high-level overexpression (>50% positive cells) of c-MYC protein (P<0.01) and high proliferation index in DLBCL (P<0.01). FISH for t(14;18) revealed 7 of 33 (21%) cases were positive for translocation and 18 (55%) had extra copies/amplification of BCL-2. The BCL-2 gene abnormalities were significantly correlated with overexpression of BCL-2 (P< 0.01), but not proliferation index.

Table 1. FISH and immunohistochemical analysis of c-myc and BCL-2 in DLBCL
C-MYCKi-67
FISHIHC, % of positive cells
Rearrangement only(n=5)80-90%80-100%
Amplification/extra copies(n=20)50-80%60-100%
Normal (n=8)0-10%(n=6)10-40%
 30-40%(n=2)10-40%
BCL-2Ki-67
FISHIHC, % of positive cells
t(14;18) only (n=7)90-100%70-100%
Amplification/extra copies(n=18)50-100%60-90%
Normal (n=8)0-10%(n=6)50-80%
 50-60%(n=2)60-80%


No significant correlation was found between c-MYC or BCL-2 expression and GCB/ABC status.
Conclusions: Amplification and gain of extra copies of MYC and BCL-2 in DLBCL are much more common than expected, and associated with overexpression of the proteins. The MYC amplification/extra copies is significantly associated with high proliferation index in DLBCL, suggesting that the extra doses of c-MYC gained through this genetic mechanism may be also associated with more aggressive behavior of DLBCL.
Category: Hematopathology

Monday, March 19, 2012 8:00 AM

Platform Session: Section C, Monday Morning

 

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