12 AK 8447-min

In 1982 Stein and coworkers identified a new molecule, CD30 (Ki-1), which is expressed by Reed-Sternberg cells of classical Hodgkin’s disease (1). CD30 is a member of the tumor necrosis factor receptor (TNF-R) superfamily (2), which comprises more than 19 different members (3). CD30 has an extracytoplasmic domain, transmembrane region, and a cytoplasmic domain. CD30 lacks death domain in the cytoplasmic trail of the protein (3). The majority of mAbs against human CD30 recognize epitopes within the extracytoplasmic domain. The protein is heavily glycosylated within the Golgi apparatus (120 kDa). A variant form (CD30v) having only the cytoplasmic domain is expressed in alveolar macrophages. CD30 has a ligand molecule (CD30L also designated as CD153), which is present on neutrophils, activated T-cells, macrophages and monocytes.
Lymphoid cells carrying viral EBV, HIV, and HTLV-1 genomes express high levels of CD30. It is not clear whether this is due to viral transactivation of CD30 or it correlates with cell activation and proliferation.
CD30 is found in activated B lymphocytes, plasma cells, T lymphocytes, NK cells (4), monocytes, large lymphoid cells in lymph node, tonsil and thymus. The fact that the CD30 molecule can mediate signals for cell proliferation or apoptosis prompted investigators to perform a systematic investigation of CD30 antigen expression in different tissues. Expression of CD30 molecules was detected in deciduas (5) and endometrial cells with decidual change, basal layer of epidermis (6), basal layer of intestinal crypts, myoepithelial cells (6) etc.

Expression of CD30 is demonstrated in a variety of lesions-benign and malignant. In many situations it cannot be blindly applied as a diagnostic marker for those entities for the reason that its expression seems to reflect different states of cellular function or activation rather than specific marker for that particular cell of origin (7).
It is assumed that the CD30-CD30 ligand interaction could have a critical pathophysiological role in malignant lymphomas, particularly Hodgkin disease, large cell anaplastic lymphomas and Burkitt lymphomas, and is also involved in activation and functioning of the T cell-dependent immune system (8). Among malignant lymphoma CD30 is expressed in classical Hodgkin’s disease (cHD), anaplastic large cell lymphoma (ALCL), anaplastic variant of diffuse large B-cell lymphoma (av-DLBCL), and CD30 positive cutaneous lymphoproliferative disorder (8) (9) (10) (11). Some cases of mycosis fungoides can have significant CD30 expression. Primary effusion lymphoma and Castleman’s disease may also be positive (association with HHV8).
Expression of CD30 has also been demonstrated in embryonal carcinoma (12) and some seminomas (mixed germ cell tumour).

Classification of malignant lymphoma and other lymphocytic lesions, (see Neoplasms). Classification of carcinomas and germ cell tumours, viz. identification of embryonal carcinoma (together with OCT3/4) (12).
CD30 has been proposed and found to be a target for immunotherapy (2). Brentuximab is a specific antibody targeting the CD30 expressing cells (13) (14).

There are currently six different antibodies designated as anti-CD30 Abs. Ki-1 is used on frozen tissue, while Ber-H2 on paraffin-embedded tissue.
Heat-induced antigen retrieval (HIER) significantly improves detection of CD30 in paraffin-embedded tissues. Fixation is important. It is much easier to detect CD30 in formalin-fixed tissues than in B5-fixed tissues (since this is just the opposite for CD15, it is important to try to sample lymph node tissue for fixation in both fixatives for optimal work up of Hodgkin’s disease).

Control Tissue
Tonsil or lymph node containing scattered CD30+ activated lymphocytes. Also follicular lymphoma with occasional weakly positive cells or a selected case of Hodgkin’s lymphoma with known weak expression of CD30 is appropriate.
Controls for B5-fixed tissue should also be fixed in B5. Strongly positive tumours (such as anaplastic large cell lymphoma) are not recommended as positive controls.

Run G1 2014

Selected references
  1. Identification of Hodgkin and Sternberg-reed cells as a unique cell type derived from a newly-detected small-cell population. Stein H, Gerdes J, Schwab U, Lemke H, Mason DY, Ziegler A, Schienle W, Diehl V. October 15, 1982, Int J Cancer, Vol. 30, pp. 445-59.
  2. CD30 (Ki-1) molecule: a new cytokine receptor of the tumor necrosis factor receptor superfamily as a tool for diagnosis and immunotherapy. Falini B, Pileri S, Pizzolo G, Dürkop H, Flenghi L, Stirpe F, Martelli MF, Stein H. 1, January 1, 1995, Blood, Vol. 85, pp. 1-14.
  3. Clinical implications of the tumor necrosis factor family in benign and malignant hematologic disorders. Anas Younes M.D., and Bharat B. Aggarwall Ph.D. August 1, 2003, Cancer, Vol. 98, pp. 458-467.
  4. Cultured human NK cells express Ki-1/CD30 antigen.Anna Cambiaggi December 22, 1992, British journal of haematology, Vol. 85, p. 270.
  5. High expression of the CD30 molecule in human decidual cells. K. Ito, T. Watanabe, R. Horie, M. Shiota, S. Kawamura, and S. Mori.. August 1994, Am J Pathol, Vol. 145, pp. 276-280.
  6. CD30 (Ki-1) molecule expression in human embryonal epithelial cells of the basal layer of the developing epidermis and epidermal buds and its potential significance for embryogenesis. Tamiolakis D, Papadoupoulos N, Venizelos I, Lambropoulou M, Tsikouras P, Koutsougeras G, Bolioti S, Tsiapali M, Karpouzis A, Kouskoukis C. September 2005, Acta Dermatovenerol Alp Pannonica Adriat, Vol. 14, pp. 85-90.
  7. Expression of CD 30 and nerve growth factor-receptor in neoplastic and reactive vascular lesions: an immunohistochemical study. P. RUDOLPH, T. LAPPE and D. SCHMIDT. 2, August 1993, Histopathology, Vol. 23, pp. 173-178.
  8. CD30 ligand, a member of the TNF ligand superfamily, with growth and activation control CD30+ lymphoid and lymphoma cells. Gruss H-J, Herrmann F5-6, February 1996, Leuk Lymphoma., Vol. 20, pp. 397-409.
  9. CD30 distribution. Immunohistochemical study on formaldehyde-fixed, paraffin-embedded Hodgkin’s and non-Hodgkin’s lymphomas.Miettinen M. November 1992, Arch Pathol Lab Med., Vol. 116, pp. 1197-201.
  10. CD30 expression in non-Hodgkin’s lymphoma. Piris M, Brown DC, Gatter KC, Mason DY. September 1990, Histopathology., Vol. 17, pp. 211-8.
  11. Primary cutaneous Ki-1(CD30) positive anaplastic large cell lymphoma in childhood. Tomaszewski MM, Moad JC, Lupton GP May 1999, J Am Acad Dermatol., Vol. 40, pp. 857-61.
  12. Germ Cell Tumors of the Ovary: An Update. Francisco F. Nogales, Isabel Dulcey, and Ovidiu Preda. March 2014, Archives of Pathology & Laboratory Medicine, Vol. 138, pp. 351-362
  13. Safety and Efficacy of Brentuximab Vedotin in Patients With Hodgkin Lymphoma or Systemic Anaplastic Large Cell Lymphoma. Christos Vaklavas, MD, Andres Forero-Torres, MD. 2012, Ther Adv Hem., Vol. 3, pp. 209-225.
  14. Brentuximab Vedotin. Dr. B. von Tresckow, A. Engert. May 2014, Der Onkologe, Vol. 20, pp. 464-469.
  15. [Online]
  16. Structure and expression of murine CD30 and its role in cytokine production. Bowen MA, Lee RK, Miragliotta G, Nam SY, Podack ER. January 15, 1996, J Immunol., Vol. 156, pp. 442-9.
  17. The TNF and TNF receptor superfamilies: integrating mammalian biology. Locksley, R.M., Killeen, N. and Lenardo, M.J.. 2001, Cell, Vol. 104, pp. 487-501.