CD31

Synonyms: platelet endothelial cell adhesion molecule 1, PECAM-1

by Assia Bassarova

Background

CD31, also known as platelet endothelial cell adhesion molecule1 (PECAM-1), is a transmembrane homophilic receptor that is expressed by endothelial cells (ECs), platelets, granulocytes, macrophages, dendritic cells (DCs), T- and B-cells and natural killer (NK) cells. As a member of the immunoglobulin (Ig) gene superfamily, CD31 comprises six extracellular Ig folds; it has a molecular mass of 130 kDa and is differentially glycosylated, involving N-linked and O-linked glycosylation sites. There are several spliced variants of CD31 – expressed in a cell-type- and species-specific manner.
In addition to its well-known homotypic or homophilic interaction, a number of putative heterotypic ligands for CD31 have also been identified, including the neutrophil-specific antigen CD177 and the ADP-ribosyl cyclase CD38.

Staining in normal cells/tissues

CD31 is exclusively expressed by cells interacting at the blood-vessel interface. Its highest expression density is found on endothelial cells (1*106 copies/cell), followed by myelo-monocytes (1*105 copies/cell), lymphocytes (1*104 copies/cell), and platelets (5*103 copies/cell). Interestingly, the prevalent localization of endothelial CD31 varies with the type of the vessel: in large vessels, where the rapid flow is parallel to the wall, the high shear stress maximally twists the endothelial cell–cell junctions and CD31 molecules are concentrated at the lateral cell borders. Instead, on microvascular endothelial cells, where the speed of the flow is minimal, the prevalent haemodynamic force is normal (perpendicular) to the wall and CD31 is maximally concentrated on the luminal and abluminal endothelial plasma membrane and in submembrane intracellular vacuoles, whereas it is present at very low density at the lateral plasma membrane.

Staining in tumors

  • CD31 is expressed in the vast majority of all types vascular neoplasms, such as different histological variants of hemangioendothelioma, angiofibroma, hemangioma, and angiosarcoma. including most cases of Kaposi sarcoma.
  • In haematopathology CD31 expression was reported in chronic lymphatic leukaemia, mycosis fungoides, plasmacytoma, histiocytosis and juvenile xantogranuloma.
  • In few reports CD31 positivity was observed in mucoepidermoid carcinoma, papillary thyroid carcinoma, sweat gland tumours, and metaplastic spindle cell breast carcinoma, but the diagnostic utility is questionable. Rare expression was documented as well in malignant mesothelioma.
  • Finally CD31 has been detected in malignant gliomas, not only in the vessels but also the neoplastic cells.

Staining pattern

Membranous.

Control tissue

Tonsil / appendix and liver are recommended as tissue controls for CD31. In tonsil, the vast majority of all mantle zone B-cells cells must have weak to moderate, but distinct membranous reactivity, while endothelial and plasma cells must show a strong, predominantly membranous staining reaction. The squamous / glandular epithelium cells should be negative. In liver, the hepatic sinusoidal endothelial cells must display weak to moderate, distinct membranous staining reaction, while hepatocytes are negative.

Application

  • CD31 is usually part of the panel for tumours with endothelial cell differentiation and should be considered a reliable marker for all types of vascular neoplasms.
  • CD31 may also be used for evaluating / counting microvessel density in tumor specimens.

Selected references

  1. Caligiuri G. Mechanotransduction, immunoregulation, and metabolic functions of CD31 in cardiovascular pathophysiology. Cardiovasc Res. 2019 Jul 1;115(9):1425-1434. doi: 10.1093/cvr/cvz132. PMID: 31119265.
  2. DeYoung BR, Swanson PE, Argenyi ZB, et al. CD31 immunoreactivity in mesenchymal neoplasms of the skin and subcutis: report of 145 cases and review of putative immunohistologic markers of endothelial differentiation. J Cutan Pathol. 1995 Jun;22(3):215-22. doi: 10.1111/j.1600-0560.1995.tb00741.x. PMID: 7593814.
  3. Feng YM, Chen XH, Zhang X. Roles of PECAM-1 in cell function and disease progression. Eur Rev Med Pharmacol Sci. 2016 Oct;20(19):4082-4088. PMID: 27775789.
  4. Jankowska-Konsur A, Kobierzycki C, Grzegrzolka J, et al. Expression of CD31 in Mycosis Fungoides. Anticancer Res. 2016 Sep;36(9):4575-82. doi: 10.21873/anticanres.11006. PMID: 27630298.
  5. Johnson EF, Davis DM, Tollefson MM, et al. Vascular Tumors in Infants: Case Report and Review of Clinical, Histopathologic, and Immunohistochemical Characteristics of Infantile Hemangioma, Pyogenic Granuloma, Noninvoluting Congenital Hemangioma, Tufted Angioma, and Kaposiform Hemangioendothelioma. Am J Dermatopathol. 2018 Apr;40(4):231-239. doi: 10.1097/DAD.0000000000000983. PMID: 29561329.
  6. Kohler S, Thiel A. Life after the thymus: CD31+ and CD31- human naive CD4+ T-cell subsets. Blood. 2009 Jan 22;113(4):769-74. doi: 10.1182/blood-2008-02-139154. Epub 2008 Jun 26. PMID: 18583570.
  7. Lertkiatmongkol P, Liao D, Mei H, et al. Endothelial functions of platelet/endothelial cell adhesion molecule-1 (CD31). Curr Opin Hematol. 2016 May;23(3):253-9. doi: 10.1097/MOH.0000000000000239. PMID: 27055047; PMCID: PMC4986701.
  8. Marelli-Berg FM, Clement M, Mauro C, et al. An immunologist’s guide to CD31 function in T-cells. J Cell Sci. 2013 Jun 1;126 (Pt 11): 2343-52. doi: 10.1242/jcs.124099. PMID: 23761922.