CD5

by Assia Bassarova

Background

The CD5 antigen is a 67 kDa transmembrane glycoprotein expressed on the surface of practically all mature human T-cells (about 10% of CD4+ T-cells being CD5 negative). In immature (CD34+) T-cells, CD5 is weakly expressed, the intensity of expression increasing with maturation. CD5 is also expressed in a small subset of normal human B-cells (20% of B-cells in the peripheral blood, scattered cells in the lymph node mantle zone). The CD5+ cells are probably involved in B-T interaction and their ligand is CD72 which is expressed on all B cells. It appears that CD5+ B-cells on activation primarily produce IgM. They also produce more autoantibodies than normal CD5 negative B-cells. Thus, the CD5+ B-cell population is expanded in rheumatoid arthritis and systemic lupus erythematosus.

Staining in normal tissues

All mature T-cells.
A subset of mature B-cells.

Staining in tumors

  • CD5 is detected in most T-cell lymphomas and leukaemias, including 75% of peripheral T-cell lymphomas and 85% of T-ALL cases. Lack of CD5 in the latter signifies a worse prognosis.
  • Among B-cell lymphomas, more explicit CD20+ small-cell lymphomas, small lymphocytic lymphoma and mantle cell lymphoma are CD5+, whereas follicular lymphoma, marginal zone lymphoma and lymphoplasmacytoid lymphoma are CD5 negative.
  • CD5 positivity seen in 5-10% of DLBCL is an independent poor prognostic factor and correlates with expression of BCL-2, MYC and high Ki67
  • CD5 is detected in 5% of acute myeloid leukemia.
  • CD5 has been detected in cases of thymic carcinoma and atypical thymoma.
  • Positivity (especially when applying clone 4C7) is reported also in 12% of nonlymphoid tumors including majority of cases of cholangiocellular carcinoma, about half of the cases of carcinoma of colon and pancreas, minority of breast, ovary, lung carcinomas and epithelioid sarcoma. Carcinomas of other organs are only rarely CD5 positive.

Staining pattern

Distinct membranous staining reaction.

Control tissue

Appendix / tonsil. Apart from strongly stained T-cells, a weaker but distinct membranous staining of about 20% of the mantle zone B-cells should be revealed.

Application

  • Useful, sensitive but not specific lymphoid marker
  • Classification of small B-cell lymphomas
  • Prognostication of T-ALL.
  • Identification of large cell lymphoma (>90% CD5 negative) supervening a CD5+ small lymphocytic lymphoma.
  • Differentiation between reactive CD5+ T-cell infiltration and CD5 negative T-cell neoplasm.
  • Identification of thymus carcinoma and thyroid carcinoma showing thymus-like elements (CASTLE)

Selected references

  1. Chu PG1, Arber DA, Weiss LM. Expression of T/NK-cell and plasma cell antigens in nonhematopoietic epithelioid neoplasms. An immunohistochemical study of 447 cases.  Am J Clin Pathol. 2003 Jul; 120(1):64-70.  doi: 10.1309/48KC-17WA-U69B-TBXQ. PMID: 12866374 DOI: 1309/48KC-17WA-U69B-TBXQ
  2. Hardy RR, Li YS, Hayakawa K. Distinctive developmental origins and specificities of the CD5+ B-cell subset. Semin Immunol. 1996 Feb;8(1):37-44. doi: 10.1006/smim.1996.0006. PMID: 8850297.
  3. Hsi ED, Said J., Macon W. R., et al. Diagnostic accuracy of a defined immunophenotypic and molecular genetic approach for peripheral T/NK-cell lymphomas. A North American PTCL study group project. (2014). The American journal of surgical pathology, 38(6), 768–775. https://doi.org/10.1097/PAS.0000000000000188
  4. Jaseb, K., Purrahman, D., Shahrabi, S., et al. Prognostic significance of aberrant CD5 expression in B-cell leukemia. Oncology reviews, (2019). 13(1), 400.https://doi.org/10.4081/oncol.2019.400
  5. Na HY, Choe JY, Shin SA, et al. Characteristicsof CD5-positive diffuse large B-cell lymphoma among Koreans: High incidence of BCL2 and MYC double-expressors. PLoS One. 2019 Oct 23; 14(10):e0224247. doi: 10.1371/journal.pone.0224247. eCollection 2019.PMID: 3164458
  6. Swerdlow, S. H., Campo, E., Pileri, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood, (2016). 127(20), 2375–2390. https://doi.org/10.1182/blood-2016-01-643569
  7. Tsuyama, N., Ennishi, D., Yokoyama, M., et al (2017). Clinical and prognostic significance of aberrant T-cell marker expression in 225 cases of de novo diffuse large B-cell lymphoma and 276 cases of other B-cell lymphomas. Oncotarget, 8(20), 33487–33500. https://doi.org/10.18632/oncotarget.16532
  8. Voisinne G., Gonzalez de Peredo A., Roncagalli, R. (2018). CD5, an Undercover Regulator of TCR Signaling. Frontiers in immunology, 9, 2900. https://doi.org/10.3389/fimmu.2018.02900
  9. Wang1, Liu B. 1,  Fan X 2, et al. Thyroid carcinoma showing thymus-like elements: a clinicopathologic, immunohistochemical, ultrastructural, and molecular analysis. Am J Clin Pathol. 2015 Feb; 143(2):223-33.  PMID: 25596248 doi: 10.1309/AJCPB7PS6QHWEFRK. DOI: 10.1309/AJCPB7PS6QHWEFRK