by Assia Bassarova
Background
CD30 was originally discovered in 1982 by Schwab and Diehl using a monoclonal antibody, Ki-1, raised against a HL-derived cell line. This antibody recognized a molecule selectively expressed by Hodgkin and Reed–Sternberg (H-RS) cells. CD30, a member of the tumor necrosis factor (TNF)-receptor family, is a membrane glycoprotein with alternate splice forms of an apparent molecular weight of 120 and 105 kDa.
CD30 has an extracytoplasmic domain, transmembrane region, and a cytoplasmic domain. The majority of mAbs against human CD30 recognize epitopes within the extracytoplasmic domain. CD30 is not usually expressed in human tissue under normal conditions, but expression is seen in thymocytes during thymus development, pancreatic exocrine cells, and decidual cells in the pregnant uterus and endometrium. A variant form (CD30v) having only the cytoplasmic domain is expressed in alveolar macrophages. CD30 is expressed by a subset of activated lymphocytes, but not on resting mature circulating T or B cells.
CD30 expression on T cells generally requires T-cell activation. During primary activation, CD30 is transiently expressed. In contrast, in secondary and subsequent activations of T cells CD30 expression is elevated and sustained, suggesting a role for CD30 in regulating memory cells together with other TNF receptor (TNFR) family members and their ligands. CD30 expression can be induced by phytohemagglutinin (PHA), or by exposure in vitro to Staphylococcus aureus, and by infection and transformation of lymphocytes by human T leukemia virus (HTLV-1 and HTLV-2) or Epstein–Barr virus (EBV).
Staining in normal cells/tissues
CD30 is found in activated B lymphocytes, plasma cells, T lymphocytes, NK cells, monocytes, large lymphoblasts in lymph nodes, tonsils, thymus. It is also expressed by decidua and endometrial cells with decidual change. Ki-1 antibody also reacted with a small population of large cells preferentially localized to reactive lymphoid tissue around B-cell follicles and medullary areas of human thymus.
Staining in tumors
Many tumors of hematolymphoid origin (varying frequency) and few non lymphoid tumors
- Lymphoid malignancies:
- Classical Hodgkin lymphoma
- Lymphomatoid papulosis
- Anaplastic large cell lymphoma (ALCL)
- Angioimmunoblastic T-cell lymphoma (AITL)
- Adult T-cell leukemia/lymphoma
- Some peripheral T-cell lymphomas
- Transformed mycosis fungoides
- Some extranodal NK/T-Cell lymphomas, nasal type
- Primary effusion lymphoma
- Mediastinal B cell lymphoma
- Minority of other B-cell lymphomas
- Aggressive systemic mastocytosis
- Mast cell leukemia
- Non-lymphoid malignancies:
- Embryonal carcinoma
- Mixed germ cell tumor
- Nasopharyngeal carcinoma (occasional)
- Minority of angiosarcomas and liposarcomas
Staining pattern
Moderate distinct membranous staining in the activated B- and T-cells. Hodgkin and Reed-Sternberg cells may also show perinuclear dot-like staining. The same staining pattern or even weak cytoplasmic staining may be also observed in mediastinal B-cell lymphoma.
Control tissue
Tonsil is recommended as positive and negative tissue control for CD30. The protocol must be calibrated to provide a weak to moderate but distinct membranous staining reaction of interfollicular activated B- and T-cells, and activated B-cells primarily located in the rim of the germinal centers. Virtually all other cells must be negative. Plasma cells, macrophages and endothelial cells may be positive depending on the primary antibody clone applied (e.g. plasma cells can be positive using the mAb Ber-H2, endothelial cells and macrophages can be positive using the mAb JCM182).
Application
- Classification of malignant lymphoma and other hematological malignancies
- Classification of carcinomas and germ cell tumors, viz. identification of embryonal carcinoma (together with OCT3/4)
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Selected references
- Berger GK, Gee K, Votruba C, et al. Potential application and prevalence of the CD30 (Ki-1) antigen among solid tumors: A focus review of the literature. Crit Rev Oncol Hematol. 2017 May;113:8-17. doi: 10.1016/j.critrevonc.2017.02.021. Epub 2017 Feb 27. PMID: 28427526.
- Chiarle, R., Podda, A., Prolla, G., et al. CD30 in Normal and Neoplastic Cells. Clinical Immunology 1999; 90(2), 157–164. doi:10.1006/clim.1998.4636
- Deutsch, Y. E., Tadmor, T., Podack, E. R., et al. CD30: an important new target in hematologic malignancies. Leukemia & Lymphoma 2011; 52(9), 1641- doi:10.3109/10428194.2011.5747
- Di Raimondo C, Parekh V, Song JY, et al. Primary Cutaneous CD30+ Lymphoproliferative Disorders: a Comprehensive Review. Curr Hematol Malig Rep. 2020 Aug;15(4):333-342. doi: 10.1007/s11899-020-00583-4. PMID: 32435988.
- Hutchinson CB, Wang E. Primary mediastinal (thymic) large B-cell lymphoma: a short review with brief discussion of mediastinal gray zone lymphoma. Arch Pathol Lab Med. 2011 Mar;135(3):394-8. doi: 10.5858/2009-0463-RSR.1. PMID: 21366467.
- Kampa F, Mitteldorf C. A review of CD30 expression in cutaneous neoplasms. J Cutan Pathol. 2021 Apr;48(4):495-510. doi: 10.1111/cup.13894. Epub 2020 Nov 6. PMID: 33047376.
- Martinez-Cabriales SA, Walsh S, Sade S, et al. Lymphomatoid papulosis: an update and review. J Eur Acad Dermatol Venereol. 2020 Jan;34(1):59-73. doi: 10.1111/jdv.15931. Epub 2019 Oct 14. PMID: 31494989.
- van Anrooij B, Kluin PM, Oude Elberink JN, et al. CD30 in systemic mastocytosis. Immunol Allergy Clin North Am. 2014 May;34(2):341-55. doi: 10.1016/j.iac.2014.01.006. Epub 2014 Mar 13. PMID: 24745678.