CD30 expression in malignancy
CD30 expression has been investigated far less in solid tumors than in hematologic malignancies, with the exception of testicular embryonal carcinoma (EC).1,2,3 Testicular embryonal carcinoma is at present the one solid tumor in which CD30 is an accepted marker of the disease and is used as part of the standard diagnostic panel. There have been occasional reports of CD30 expression in various tumors of mesenchymal origin,4,5 cutaneous angiosarcoma,6,7 nasopharyngeal non-keratinizing carcinoma8 and other solid tumors,9 though the data are inconsistent and often not reproducible. In both solid tumors and hematologic malignancies, problems assessing CD30 expression include the evolution of diagnostic criteria over the years, use of different antibodies (eg, Ki-1 vs Ber-H2), use of frozen samples vs paraffin blocks, possible differences in the percentage of cells used to indicate positivity and incomplete data reporting. Standardization of protocols and reporting practices would substantially increase understanding of the expression and possible role of CD30 in these malignancies.
Various levels of CD30 expression have been reported in many tumor types. However, with the exceptions of HL, ALCL and testicular embryonal carcinoma, CD30 expression is generally supported by only a few studies with small numbers of patients. Additional studies are needed to determine whether this activation marker is instrumental in the malignant process or just a bystander, and whether CD30 expression affects clinical prognosis. Further characterizing the cell surface expression of CD30 might help identify subtypes or variants with clinical or prognostic significance. Finally, further characterization of CD30 may enable a better understanding of the pathogenesis of cancer, particularly the lymphomas.
CD30 was initially identified on the Reed-Sternberg (R-S) cells characteristic of HL.10 The German Hodgkin Study Group and others have found CD30 in >95% of cases of classical HL.11 In contrast, CD30 is expressed less intensely and in less than 10% of cases of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), a histologic subtype that represents approximately 5% of all HL.12,13,14 CD30 is also highly expressed in ALCL.15,16 Cutaneous CD30-positive T-cell lymphoproliferative disorders, defined as having >75% of cells positive for CD30, include primary cutaneous anaplastic large cell lymphoma and lymphomatoid papulosis.17,18 CD30 expression has been studied extensively in HL and ALCL, but far less in other tumors. Some investigators have detected CD30, in different patterns and intensities, in several hematologic malignancies, including various T-cell lymphomas, subsets of B-cell lymphomas, immunoblastic lymphoma, multiple myeloma and adult T-cell lymphoma/leukemia.17,19 The literature reports CD30 expression on many T-cell15 and B-cell20 malignancies. Approximately 30% of T-cell and 15%-20% of B-cell lymphomas express CD30.21 In some of these tumor types, there is considerable support for CD30 expression, such as in peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS)22 and enteropathy-associated T-cell lymphoma.23 In others, such as multiple myeloma and acute myeloid leukemia/granulocytic sarcoma, there are small series or sometimes only case reports, underlining the need for more research in this area.24,25,26
- Latza U, Foss H-D, Dürkop H, et al. CD30 antigen in embryonal carcinoma and embryogenesis and release of the soluble molecule. Am J Pathol. 1995;146(2):463-471.
- Gopalan A, Dhall D, Olgac S, et al. Testicular mixed germ cell tumors: a morphological and immunohistochemical study using stem cell markers, OCT3/4, SOX2 and GDF3, with emphasis on morphologically difficult-to-classify areas. Mod Pathol. 2009;22(8):1066-1074.
- Dürkop H, Foss H-D, Eitelbach F, et al. Expression of the CD30 antigen in non-lymphoid tissues and cells. J Pathol. 2000;190(5):613-618.
- Mechtersheimer G, Möller P. Expression of Ki-1 antigen (CD30) in mesenchymal tumors. Cancer. 1990;66(8):1732-1737.
- Mariño-Enríquez A, Wang W-L, Roy A, et al. Epithelioid inflammatory myofibroblastic sarcoma: an aggressive intra-abdominal variant of inflammatory myofibroblastic tumor with nuclear membrane or perinuclear ALK. Am J Surg Pathol. 2011;35(1):135-144.
- Aggerholm-Pedersen N, Bærentzen S, Holmberg Jørgensen JP, Safwat A. A rare case of CD30+, radiation-induced cutaneous angiosarcoma misdiagnosed as T-cell lymphoma. J Clin Oncol. 2011;29(13):e362-e364.
- Weed BR, Folpe AL. Cutaneous CD30-positive epithelioid angiosarcoma following breast-conserving therapy and irradiation: a potential diagnostic pitfall. Am J Dermatopathol. 2008;30(4):370-372.
- Kneile JR, Tan G, Suster S, Wakely PE Jr. Expression of CD30 (Ber-H2) in nasopharyngeal carcinoma, undifferentiated type and lymphoepithelioma-like carcinoma: a comparison study with anaplastic large cell lymphoma. Histopathology. 2006;48(7):855-861.
- Schwarting R, Gerdes J, Dürkop H, Falini B, Pileri S, Stein H. BER-H2: a new anti–Ki-1 (CD30) monoclonal antibody directed at a formol-resistant epitope. Blood. 1989;74(5):1678-1689.
- Schwab U, Stein H, Gerdes J, et al. Production of a monoclonal antibody specific for Hodgkin and Sternberg-Reed cells of Hodgkin’s disease and a subset of normal lymphoid cells. Nature. 1982;299(5878):65-67.
- von Wasielewski R, Mengel M, Fischer R, et al. Classical Hodgkin’s disease: clinical impact of the immunophenotype. Am J Pathol. 1997;151(4):1123-1130.
- Uherova P, Valdez R, Ross CW, Schnitzer B, Finn WG. Nodular lymphocyte predominant Hodgkin lymphoma: an immunophenotypic reappraisal based on a single-institution experience. Am J Clin Pathol. 2003;119(2):192-198.
- von Wasielewski R, Werner M, Fischer R, et al. Lymphocyte-predominant Hodgkin’s disease: an immunohistochemical analysis of 208 reviewed Hodgkin’s disease cases from the German Hodgkin Study Group. Am J Pathol. 1997;150(3):793-803.
- Diehl V, Sextro M, Franklin J, et al. Clinical presentation, course, and prognostic factors in lymphocyte-predominant Hodgkin’s disease and lymphocyte-rich classical Hodgkin’s disease: report from the European Task Force on Lymphoma Project on Lymphocyte-Predominant Hodgkin’s Disease. J Clin Oncol. 1999;17(3):776-783.
- Stein H, Mason DY, Gerdes J, et al. The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells. Blood. 1985;66(4):848-858.
- Stein H, Foss H-D, Dürkop H, et al. CD30+ anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features. Blood. 2000;96(12):3681-3695.
- de Leval L, Gaulard P. CD30+ lymphoproliferative disorders. Haematologica. 2010;95(10):1627-1630.
- Willemze R, Jaffe ES, Burg G, et al. WHO-EORTC classification for cutaneous lymphomas. Blood. 2005;105(10):3768-3785.
- Younes A, Kadin ME. Emerging applications of the tumor necrosis factor family of ligands and receptors in cancer therapy. J Clin Oncol. 2003;21(18):3526-3534.
- Noorduyn LA, de Bruin PC, van Heerde P, van de Sandt MM, Ossenkoppele GJ, Meijer CJLM. Relation of CD30 expression to survival and morphology in large cell B cell lymphomas. J Clin Pathol. 1994;47(1):33-37.
- Falini B, Pileri S, Pizzolo G, et al. CD30 (Ki-1) molecule: a new cytokine receptor of the tumor necrosis factor receptor superfamily as a tool for diagnosis and immunotherapy. Blood. 1995;85(1):1-14.
- Savage KJ, Harris NL, Vose JM, et al; International Peripheral T-Cell Lymphoma Project. ALK- anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK+ ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International Peripheral T-Cell Lymphoma Project. Blood. 2008;111(12):5496-5504.
- Delabie J, Holte H, Vose JM, et al. Enteropathy-associated T-cell lymphoma: clinical and histological findings from the International Peripheral T-Cell Lymphoma Project. Blood. 2011;118(1):148-155.
- Menke DM, Horny H-P, Griesser H, Atkinson EJ, Kaiserling E, Kyle RA. Immunophenotypic and genotypic characterisation of multiple myelomas with adverse prognosis characterised by immunohistological expression of the T cell related antigen CD45RO (UCHL-1). J Clin Pathol. 1998;51(6):432-437.
- Gattei V, Degan M, Gloghini A, et al. CD30 ligand is frequently expressed in human hematopoietic malignancies of myeloid and lymphoid origin. Blood. 1997;89(6):2048-2059.
- Fickers M, Theunissen P. Granulocytic sarcoma with expression of CD30. J Clin Pathol. 1996;49(9):762-763.