R4 簡聖軒
指導老師: 高志平大夫
Maturation of B lymphocyte
 DLBCL classification
 Double hit DLBCL
 MYC/BCL-2 co-expression DLBCL
 Conclusion and take home message
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Common morphologic variants
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Centroblastic/immunoblastic/anaplastic
Rare morphologic variants
Molecular subgroups
Germinal centre B cell like(GCB)
 Activated B cell like (ABC)
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Immnuohistochemical subgroup
CD-5 (+) DLBCL
 Germinal centre B cell like (GCB)
 Non-germinal centre B cell like (non-GCB)
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Nature 2000, 403:503-511
GCB: BCL6, CD 10
 ABC: MYC, MUM1, CD44, FLIP, cyclin D2
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Nature 2000, 403:503-511
•16 case
•From 1998-2006
•CD20, CD10, Bcl-6, Mum-1, Bcl-2 CD138, MIB1, CD19, CD5, CD38
•DLBCL with a germinal center (GC) profile.
•Progression free survival : 4 months
•Over all survival : 5 months
Haematologica :92; 10, 1335-1342, 2007
Chromosome breaks targeting the MYC gene
located at the 8q24 in combination with
additional rearrangement, such as BCL2,BCL6
 MYC/BCL2 double hit lymphoma
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extremely poor prognosis
 Most GCB type
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Haematologica :92; 10, 1335-1342, 2007
•307 cases (167 in training /140 in validation center)
• Detected MYC, BCL-2 by IHC
•MYC correlated with high MYC mRNA and MYC translocation
•Co expression of MYC and BCL-2 protein had inferior outcome
Reviewed 893 cases
 Tissue microarray immunohistochemical stain
 FISH for MYC, BCL-2 and sequencing TP53
 Gene expression profiling
 COO classification: combined with GEP+IHC
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64% MYC(+), 50% BCL-2(+)
 34% MYC(+) + BCL-2(+)
 19% MYC(-) + BCL-2(-)
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MYC+BCL2
Others
P
5-yr OS
30%
75%
<0.0001
5-yr PFS
27%
73%
<0.0001
GCB
ABC
•208 genes express
differentially P<0.001
•GCB:
CD10
BCL-6
MYBL1
PI3KCG
•ABC:
MUM1
cyclin D2
FLIP
CD44
SLAP
•No significant difference
as P <0.001
•20 gene express
differentially as P <0.01
•13/20 gene also express in
MYC/BCL-2(+) COO
differentially
Total 153 genes were differentially expressed (P<0.001)
65 genes up-regulated
88 genes down-regulated
5-yrs OS/PFS <30 % in MYC/BCL coexpression
 Correlated with poor prognosis factor: older age,
advanced stage, extra-nodal, high IPI
 29% DLBCL, expand the spectrum of
aggressive DLBCL via IHC VS 3% double hit
via genetic level
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MYC/BCL-2 co-expression is more frequently
observed in ABC subtype
 MYC/BCL-2 co-expression contributes to the
overall poor prognosis of this patient subset
1. Excluded MYC/BCL-2 (+), ABC ≒GCB
2. In MYC/BCL-2 (+), ABC ≒GCB
3. Difference in gene signatures between 2
subtypes was minimal in MYC/BCL-2 (-)
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DLBCL is heterogeneous group
 MYC/BCL-2 co-expression identified by IHC:
poor prognosis, expand the spectrum of
MYC/BCL-2 double hit in gene rearrangement
 Assessment for MYC and BCL-2 protein
expression more reliably predicts prognosis than
COO classification
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