pax-5

The pax-5 gene is essential for B-cell differentiation. There are at least four isoforms, of which pax-5a has been most studied. Pax-5  encodes the 50 kDa B-cell specific activator protein, BSAP. Pax-5 is expressed by pro-, pre- and mature B cells, but is downregulated during terminal differentiation of plasma cells. Pax-5 influences the expression of other B-cell specific genes, including CD19 and CD20 and CD79a, preceding the expression of CD20. Pax-5 is silenced at the plasma cell stage under the influence of B-lymphocyte-induced maturation protein-1 (PRDM1)5.

Pax-5 is expressed during mouse embryogenesis within the developing brain in a way that is temporarily and spatially tightly condoled. Pax-5 deficient mice show deformation of the mid-brain. Expression in human embryogenesis occurs in the mesoencephalon and spinal cord6.

Antibodies are reactive in formalin-fixed paraffin-embedded tissue. Immunoreactivity is nuclear.

Immunohistochemical expression

• squamous epithelium2,6, skin appendages6, endothelial cells6, fibroblasts6 and other stromal cells6, respiratory epithelium6 and pneumocytes6 are all negative.

• There is positivity in the epithelium of the rete testis and epididymis.

• Non-neoplastic lymphoid tissue showed the same distributions for pax-5 and CD20 immunoreactivity. There is positivity of germinal centres, mantle zone (strong), monocytoid B-cells (weak), and intra-epithelial lymphocytes2. Interfollicular blasts have variously been reported as positive2 and negative3. Bone marrow showed additional pax-5 positivity due to reactivity of hematogones. In B-cell lymphomas, there appears to be an excellent combination of sensitivity and specificity. Note that some studies used monoclonal1,2 and some polyclonal3 antibodies; the latter may be less sensitive. Results for CD20 on the same cases are given for comparison:

• Pax-5 is commonly expressed by Merkel cell carcinoma and small cell carcinoma, two small blue round cell tumours that appear in the differential diagnosis of lymphoma, but not in other small blue round cell tumours6:

•  

• Pax-5 and pax-6 are expressed by about 70% of medulloblastomas as detected by Northern blot analysis7.

• Positive in alveolar rhabdomyosarcoma but not its mimics:

Diagnostic utility

Identification of B-cell lymphomas including:

• the detection of pre-B cells, where it serves as a surrogate of CD19. All cells committed to B-cell lineage express Pax-5, including those mixed lineage acute lymphoblastic leukemia that are positive for CD19. However, note that other small round blue cell tumours such as Merkel cell carcinoma and small cell carcinoma may be immunoreactive.

• the differentiation of Classical Hodgkin lymphoma (positive for pax-5) from T and "null" cell anaplastic large cell lymphoma (negative for pax-5).

• the differentiation of lymphoplasmacytic lymphoma/plasmacytoid differentiation in B-CLL, lymphoplasmacytic lymphoma/Waldenstrom macroglobulinaemia and mucosa associated lymphoid tissue lymphoma (positive for pax-5) from plasma cell myeloma (negative for pax-5). However, care needs to be take with the minority of myelomas that are CD20+/Pax-5+5.

• The diagnosis of (translocation-positive) alveolar rhabdomyosarcoma.

References

1 Torlakovic, E., G. Torlakovic, et al. “The value of anti-pax-5 immunostaining in routinely fixed and paraffin- embedded sections: a novel pan pre-B and B-cell marker.” Am J Surg Pathol 2002; 26(10): 1343-50. with clarificatrions kindly provided by Dr Torlakovic.

2 Foss, H. D., R. Reusch, et al. (1999). “Frequent expression of the B-cell-specific activator protein in Reed- Sternberg cells of classical Hodgkin's disease provides further evidence for its B-cell origin.” Blood 94(9): 3108-13.

3 Krenacs, L., A. W. Himmelmann, et al. (1998). “Transcription factor B-cell-specific activator protein (BSAP) is differentially expressed in B cells and in subsets of B-cell lymphomas.” Blood 92(4): 1308-16.

4 Torlakovic, E., A. Tierens, et al. (2001). “The transcription factor PU.1, necessary for B-cell development is expressed in lymphocyte predominance, but not classical Hodgkin's disease.” Am J Pathol 159(5): 1807-14.

5 Lin, P., M. Mahdavy, et al. (2004). "Expression of PAX5 in CD20-positive multiple myeloma assessed by immunohistochemistry and oligonucleotide microarray." Mod Pathol 17(10): 1217-22.

6 Dong HY, Liu W, Cohen P, et al. B-cell specific activation protein encoded by the PAX-5 gene is commonly expressed in merkel cell carcinoma and small cell carcinomas. Am J Surg Pathol 2005; 29:687-92

7 Kozmik Z, Sure U, Ruedi D, et al. Deregulated expression of PAX5 in medulloblastoma. Proc Natl Acad Sci U S A 1995; 92:5709-13

8 Sullivan LM, Atkins KA,LeGallo RD. PAX immunoreactivity identifies alveolar rhabdomyosarcoma. Am J Surg Pathol 2009; 33:775-80

This page last revised 21.5.2009.

©SMUHT/PW Bishop