CD30 Cross-Reactivity and Expression in Feline Normal Tissues and Lymphomas

Abstract

CD30 is a transmembrane glycoprotein of the tumor necrosis factor receptor superfamily included in the diagnostic algorithm of human cutaneous, anaplastic large cell and Hodgkin lymphomas and represents an optimal therapeutic target for CD30+ tumors. Similar diagnostic and therapeutic approaches are largely missing for feline lymphomas. Cross-reactivity of the antihuman CD30 receptor clone Ber-H2 was investigated in feline lymphomas. Comparative analysis of feline and human CD30 identified 61% identity of the amino acid sequence, with 100% identity of the main sequence of the epitope targeted by the antibody (RKQCEPDYYL). CD30 expression in normal feline tissues was restricted to rare lymphoid cells in perifollicular and interfollicular lymph node areas and in the thymic medulla. In feline lymphoma, CD30 was expressed in 4 of 33 (13%) T-cell lymphomas, 3 of 22 (14%) B-cell lymphomas, and 5 of 7 (71%) mixed-cell lymphomas, showing diffuse (1/5) or multifocal (4/5) positivity restricted to neoplastic multinucleated lymphoid cells and binucleated cells consistent with Reed-Sternberg-like cells. Based on the human classification system, cell morphology, expression of multiple markers (mixed cell components), and CD30 positivity, these cases were considered most consistent with classical Hodgkin-like lymphoma (HLL). The other 2 mixed-cell lymphomas were CD30 negative and thus most consistent with either T-cell-rich large B-cell lymphoma (TCRLBCL) or nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). These findings provide multiple data supporting the cross-reactivity of the Ber-H2 anti-CD30 clone in feline tissues and give evidence of the usefulness of CD30 in the diagnostic evaluation of feline lymphoma.

Intraepithelial cytotoxic lymphocytes are associated with a poor prognosis in feline intestinal T-cell lymphoma

“…The reactivities of CD8, granzyme B, CD30, CD56, and FOXP3 were confirmed in the following articles. 4,21,27,32,39 Sequence alignment of human and feline TIA1 was obtained from The Universal Protein Resource (UniProt) (Supplemental Fig. S1).…”

Validating Immunohistochemistry Assay Specificity in Investigative Studies: Considerations for a Weight of Evidence Approach

“…5 This approach was used in evaluating an anti-human CD30 antibody in feline tissues. 4 Unfortunately, an antibody that works well in one species, will not always perform similarly in a different species. 35 An example of this is melan A, which is a commonly used marker for canine melanoma.…”

“…An example of this is a study that evaluates an antibody in a series of tumors that are expected to express or not express the protein of interest. 4,39,40 These studies define the diagnostic utility and interpretation of an IHC assay; however, they do not always test the specificity of the antibody for its cognate epitope. Frequently, characterization of an antibody’s specificity for its target protein requires additional steps that may or may not be practical given the purpose of the assay.…”

Anti‐CD30 (Ber‐H2) epitope requires structural elements as shown by mass spectroscopy and dual‐site associated kinetics

“…Anti‐CD30 antibodies have diagnostic utility in detecting a protein expressed by Hodgkin and Reed‐Sternberg (HRS) cells in Hodgkin's lymphoma, primary cutaneous T‐cell lymphoproliferative disorders, anaplastic large cell lymphomas, embryonal carcinomas, 1‐3 and feline lymphomas 4 . HRS cells are large, often multi‐nucleated lymphocytes that are the hallmark tumor cells of Hodgkin's lymphoma.…”