CD 30

Accurate (Ki-1, Ber-H2), Biodesign (HRS4), Bioprobe (IC)-88), Cymbus Bioscience (Ki-1), Dako (Ber-H2, Ki-1), Diagnostic Biosystems (Ki-1, Ber-H2), Immunotech (HRS4, Ki-1) and Serotec.

The Ki-1 antibody produces membrane staining only in frozen sections and does not stain paraffin-embedded tissues. BER-H2 labels an epitope that survives routine fixation and processing.

The first CD 30 antibody to be generated was called Ki-1 and was thought to be specific for Reed-Sternberg cells. The Ki-1 antibody recognizes an intracellular protein and a membrane-bound glycoprotein which are apparently not related. The membrane-bound glycoprotein is often referred to as the true CD 30 antigen. It has a molecular mass of 105-120 kD and is phosphorylated at serine residues and contains an N- and O-glycosidyl bound carbohydrate portion. The extracellular domain of CD 30 shows significant homology with members of the tumor necrosis factor/nerve growth factor receptor superfamily (Stein et al, 1985). The human CD 30 gene has been localized to the short arm of chromosome 1 at 1p36, a band frequently involved in neoplastic disorders (Fonatsch et al, 1992). Deletions, duplications, translocations and inversions of this band have been observed in non-Hodgkin's lymphomas and abnormalities of the short arm of chromosome 1 have been described in Hodgkin's disease. 1p36 is also the location for the TNF receptor-2 gene and appears to be a preferential site for integration of viruses such as the Epstein-Barr virus.
CD 30 appears to be a lymphoid activation antigen and its expression can be induced on B and T lymphocytes in vitro by a number of stimuli which include viruses and lectins. CD 30 may act as a receptor whose ligand is a cytokine. Recombinant CD 30L exhibits pleiotropic cytokine activities, with CD 30L inducing proliferation of activated T cells in the presence of an anti-CD 3 costimulus and enhancing the proliferation of a Hodgkin's cell line HDLM2. CD 30L mRNA expression can be induced on Tcells and macrophages, suggesting that a variety of autocrine and paracrine mechanisms may be operative. Immunoelectron microscopic studies have localized the antigen in the cytoplasm and in association with the nuclear envelope, chromatin structures and nucleoli.

CD 30 antibodies do not react against any resting peripheral blood cells. Staphylococcus-stimulated B lymphocytes and phytohemagglutinin-stimulated T lymphocytes become CD 30+, and expression of the antigen can be induced by activating T-helper lymphocytes with autologous and allogeneic stimulator cells. The antigen is also expressed in Epstein-Barr virus-transformed B cells and human T lymphotrophic virus-transfected T-cell lines. Activated T-cells express CD 38, CD 71, CD 25, epithelial membrane antigen, HLA-DR and CD 15 together witha-1-antitrypsin and CD 11C prior to the expression of CD 30. Scattered large B and T cells localized around lymphoid follicles and at the margin of germinal centers show CD 30 positivity in normal and reactive lymph nodes. These cells may also coexpress Ki-67 nuclear antigen, indicating their proliferating state. Similarly, macrophages which are generally negative for CD 30 may become CD30+ in conditions such as miliary tuberculosis, sarcoidosis and other granulomatous reactions such as cat scratch disease and toxoplasmosis. BER-H2 may also label a subpopulation of plasma cells. Among non-hemopoietic tissues, exocrine pancreatic cells, some cerebral cortical neurons and Purkinje cells may be positive for CD 30.
In initial studies, Hodgkin's disease was the only neoplasm that was CD30+. About 89% of cases of non-lymphocyte predominant Hodgkin's disease are positive for CD 30 and the staining pattern is membranous, often with a strong paranuclear globule in the region of the Golgi and weaker cytoplasmic staining. In frozen sections, BER-H2 produces stronger staining than Ki-1 and staining is also stronger in frozen sections than in paraffin sections. A variable degree of positivity is seen in the L&H cells of lymphocyte-predominant Hodgkin's disease. About 25% of cases show positivity in paraffin sections and the staining is generally weaker and is limited usually to the cell membrane (Swerdlow & Wright, 1986). It is reported that a much higher incidence of positivity is seen in frozen sections.
CD 30 expression is a characteristic of anaplastic large cell lymphoma (ALCL) which is defined in part by its nearly constant CD 30 positivity. The pattern of staining is similar to that seen in Reed-Sternberg cells and may be expressed by ALCLs of both T- and B-cell lineage as well as "null" cell types. CD 30 expression, however, is not limited to ALCL and may be found in other types of non-Hodgkin's lymphoma. In one study of about 500 cases of non-Hodgkin's lymphomas, 36 cases of lymphomas other than ALCL were CD 30+. The expression of CD 30 is highest in immunoblastic lymphomas, and among the T-cell lymphomas both mycosis fungoides as well as other types of peripheral T-cell lymphomas including AILD-like T-cell lymphoma, Lennert's lymphoma and HTLV-I+ T-cell leukemia/lymphoma, may show a relatively high incidence of CD 30 positivity. It has been suggested that primary CD30+ lymphomas, particularly primary cutaneous lymphomas, have a better prognosis than their CD 30-counterparts (Stein et al, 1985; Piris et al, 1990). However, the expression of CD 30 in cutaneous lymphomas which arise in patients with a preceding history of another lymphoma may have a particularly poor prognosis. The expression of CD 30 in lymphomatoid papulosis and regressing atypical histiocytosis has suggested a close relationship between these disorders and cutaneous CD 30+ ALCL. These three lesions may represent a spectrum with their histologic and clinical characteristics determined by the degree of biological aggressiveness of the neoplasm and the host immune defenses.
Occasional cases of plasmacytomas and myelomas may show CD 30 positivity. Hairy cell leukemia is consistently negative for CD 30 and Langerhans' cell histiocytosis is also CD 30-. Staining has also been reported to be negative in three cases of dendritic reticulum cell sarcoma and the expression in true histiocytic tumors is not known. CD 30 positivity has not been reported in cases of leukemia (Piris et al, 1990).
CD 30 positivity has been reported in embryonal carcinomas and in the embryonal elements of mixed germ cell tumors and, less commonly, has been observed in pancreatic and salivary gland carcinomas (Pallesen & Hamilton-Dutoit, 1988). Occasionally, other paraffin-embedded carcinomas and malignant lymphomas may show weak, diffuse cytoplasmic staining and CD 30 positivity has more uncommonly been observed in mesenchymal tumors including leiomyoma, leiomyosarcoma, rhabdomyosarcoma, synovial sarcoma, giant cell tumor of tendon sheath, malignant fibrous histiocytoma, osteogenic sarcoma, Ewing's sarcoma, malignant schwannoma, ganglioneuromas and aggressive fibromatosis. Occasional lipoblasts in liposarcoma may show positivity (Mechterscheimer & Moller, 1990; Chang et al, 1993).

We have found that BER-H2 staining is enhanced by MW epitope retrieval in citrate buffer with or without enzyme pretreatment. Because it is expressed in stimulated B-and T-lymphoid cells, BER-H2 should not be employed as a primary marker of Reed-Sternberg cells. However, it should be used in a panel for the identification of ALCL, bearing in mind that such tumors may be CD 45- and EMA+, an immunophenotype which may be mistaken for carcinoma. From a practical standpoint, ALCLs do not express cytokeratin. express cytokeratin.

•Chang KL, Arber DA, Weiss LM 1993. CD30: a review. Applied Immunohistochemistry 1: 244-255.

•Fonatsch C, Latza U, Durkop H, et al 1992. Assignment of the human CD30 (Ki-1) gene to 1p36. Genomics 14: 825-826.

•Mechterscheimer G, Moller P 1990. Expression of Ki-1 antigen (CD30) in mesenchymal tumours. Cancer 66: 1732-737.

•Pallesen G, Hamilton-Dutoit SJ 1988. Ki-1 (CD30) antigen is regularly expressed by tumour cells of embryonal carcinoma. American Journal of Pathology 133: 446-450.

•Piris M, Brown DC, Gatter KC, Mason DY 1990. CD30 expression in non-Hodgkin's lymphoma. Histopathology 17: 211-18.

•Stein H, Mason DY, Gerdes J et al 1985. The expression of the Hodgkin's disease-associated antigen Ki-1 in reactive and neoplastic lymphoid tissues. Evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells. Blood 66: 848-858.

•Swerdlow SH, Wright SA 1986. A spectrum of LeuM1 staining in lymphoid and haemopoietic proliferations. American Journal of Clinical Pathology 85: 283-288.

Manual of diagnostic antibodies for immunohistology / Anthony S.-Y. Leong, Kumarasen Cooper, F. Joel W.-M. Leong.