bcl-6

The bcl-6 gene is located at 3q275. Bcl-6 is a 79-kDa POZ/zinc finger transcriptional repressor3. It plays a role in the activation and proliferation of B cells within the germinal centre4. It is therefore a marker for germinal centre cells and their derivative lymphomas, particularly if there is no gene rearrangement to account for the activation1. BCL-6 represses many lymphocyte activation genes, including blimp-1. Since blimp-1 plays a role in plasma cell differentiation, bcl-6 may play a role in malignant transformation by the inhibition of differentiation7. Over-expression of bcl-6 results in delayed progression through the S phase of the cell cycle or apoptosis. Bcl-6 activation occurs by translocations involving immunoglobulin light or heavy chain genes, which occurs in one third of diffuse large B cell lymphoma, or by mutation in the 5 non-coding region.

Immunoreactivity is nuclear.

Immunohistochemical expression

 

 

bcl-6

CD10

 

Follicular hyperplasia

19/19

19/19

Nodal follicular lymphoma

28/28

36/39

Splenic follicular lymphoma

6/7

4/11

MALT lymphoma

0/17

0/24

Mantle cell lymphoma

0/18

0/19

Splenic marginal zone lymphoma

0/10

0/13

Diffuse large B cell lymphoma

39/476

21/546

10 cases had evidence of previous follicular lymphoma: all but one were positive for both bcl-6 and CD106. Of 44 DLBCL, NOS6:

 

CD10+

CD10-

bcl-6+

11

1

bcl-6-

21

11

Burkitt lymphoma

17/176

20/206

CD30+ ALCL

12/279

 

peripheral T-cell lymphoma

0/249

 

T-lymphoblastic leukaemia

0/89

 

NLPHD

11/13

0/166

Classical HD

4/8

0/136

     

 

Diagnostic utility

As a marker for follicle centre B-cells, along with CD10. Follicular lymphomas are positive for both bcl-6 and CD10, while other low grade lymphomas which may have a follicular growth pattern, particularly mantle cell lymphoma and marginal zone lymphoma (in which follicles may be colonised), are negative.

References

1 de Leval, L., Ferry, J. A., Falini, B., Shipp, M., Harris, N. L. Expression of bcl-6 and CD10 in primary mediastinal large B-cell lymphoma: evidence for derivation from germinal center B cells? Am J Surg Path 2001;25:1277-1282.

2 Falini. Blood 1996;87:465-471.

3 Petitjean, B., Jardin, F., Joly, B., Martin-Garcia, N., Tilly, H., Picquenot, J.M., Briere, J., Danel, C., Mehaut, S., Abd-Al-Samad, I., Copie-Bergman, C., Delfau-Larue, M.H. and Gaulard, P. Pyothorax-associated lymphoma: a peculiar clinicopathologic entity derived from B cells at late stage of differentiation and with occasional aberrant dual B- and T-cell phenotype. Am J Surg Pathol 2002;26:724-32.

4 Leoncini, L., Lazzi, S., Bellan, C. and Tosi, P. Cell kinetics and cell cycle regulation in lymphomas. J Clin Pathol 2002;55:648-55.

5 Camacho, F. I., J. F. Garcia, et al. (2004). "Aberrant Bcl6 protein expression in mantle cell lymphoma." Am J Surg Pathol 28(8): 1051-6.

6 Dogan A, Bagdi E, Munson P, et al. CD10 and BCL-6 expression in paraffin sections of normal lymphoid tissue and B-cell lymphomas. Am J Surg Pathol 2000; 24:846-52

7 Shaffer AL, Yu X, He Y, et al. BCL-6 represses genes that function in lymphocyte differentiation, inflammation, and cell cycle control. Immunity 2000; 13:199-212

8 Kraus MD,Haley J. Lymphocyte predominance Hodgkin's disease: the use of bcl-6 and CD57 in diagnosis and differential diagnosis. Am J Surg Pathol 2000; 24:1068-78

9 Carbone A, Gloghini A, Gaidano G, et al. BCL-6 protein expression in human peripheral T-cell neoplasms is restricted to CD30+ anaplastic large-cell lymphomas. Blood 1997; 90:2445-50 FULL TEXT

 

This page last revised 13.7.2005.

©SMUHT/PW Bishop