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PAX5

MIM.167414 9p13

Wednesday 11 May 2005

Definition: PAX5 is a B cell specific transcription factor crucial for B cell ontogeny and has been detected in most of human B-cell lymphomas.

Images

- PAX5+ vulvar CLL/SLL infiltrate (chronic lymphocytic leukemia / small lymphocyte lymphoma )

- PAX5 in classic Hodgkin lymphoma

PAX5 is a member of the paired box transcription factors involved in development and its expression has been well characterized among hematopoietic malignancies of B-cell lineage.

Its expression has also been reported in a subset of neuroendocrine carcinomas, urothelial tumors, Merkel cell carcinoma, glioblastoma, and neuroblastoma cell lines.

No other tumor type is immunoreactive toward PAX5.

PAX5 gene encodes a B-cell-specific activator protein (BSAP) that binds to promoters of the CD19 gene, B cell-specific tyrosine kinase gene BLK (MIM.191305), and to regulatory regions of the immunoglobulin heavy chain locus, including sequences implicated in Ig class switching.

In mouse, PAX5 is also highly expressed in the central nervous system under tight temporal and spatial controls during embryogenesis. In humans, however, detection of PAX5 in cells other than B lymphocytes has rarely been reported.

Expression in tumors

- B-cell lymphomas
- Merkel cell carcinoma (93.5%) (15832095)
- neuroendocrine small cell carcinoma (73.3%) (15832095)
- alveolar rhabdomyosarcoma (ARMS) (67%)

All B-cell lymphoblastic lymphomas are strongly immunoreactive against PAX5.

Additionally, all Wilms tumors show staining of variable intensity, most intensely in the epithelial component.

Of the rhabdomyosarcoma cases, 67% ARMS are immunoreactive whereas none of the embryonal rhabdomyosarcoma stained.

PAX3 and PAX7 fusion genes characterize the majority of ARMS making crossreactivity with these proteins an attractive theory, and suggest that PAX5 immunoreactivity may be specific for translocation-positive ARMS.

Pathology

- PAX5 rearrangements

  • PAX5/IGH rearrangement by t(9;14)(p13;q32) (9p13 and 14q32) in 50% of lymphoplasmacytic lymphoma

- germline PAX5 mutation

  • A recurrent germline PAX5 mutation confers susceptibility to pre-B cell acute lymphoblastic leukemia, August 2013. doi : 10.1038/ng 2754

See also

- PAXs

References

- A recurrent germline PAX5 mutation confers susceptibility to pre-B cell acute lymphoblastic leukemia. Shah S, Schrader KA, Waanders E et al. Nat Genet. 2013 Oct;45(10):1226-31. doi : 10.1038/ng.2754 PMID: 24013638

- PAX immunoreactivity identifies alveolar rhabdomyosarcoma. Sullivan LM, Atkins KA, LeGallo RD. Am J Surg Pathol. 2009 May;33(5):775-80. PMID: 19145202

- Rare lymphoid neoplasms coexpressing B- and T-cell antigens. The role of PAX-5 gene methylation in their pathogenesis. Lazzi S, Bellan C, Onnis A, De Falco G, Sayed S, Kostopoulos I, Onorati M, D’Amuri A, Santopietro R, Vindigni C, Fabbri A, Righi S, Pileri S, Tosi P, Leoncini L. Hum Pathol. 2009 Apr 13. PMID: 19368954

- Dong HY, Liu W, Cohen P, Mahle CE, Zhang W. 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 May;29(5):687-92. PMID: 15832095

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