Targeting CD30 in Malignant Tissues: Challenges in Detection and Clinical Applications

Abstract

The CD30 transmembrane receptor from the tumor necrosis factor receptor family is expressed in a distinct, yet diverse set of lymphoproliferative disorders and a small subset of normal activated lymphocytes. Therefore, detection of CD30 expression when performed properly according to the standardized methods facilitates diagnosis of Hodgkin lymphoma, anaplastic large cell lymphoma, and other disorders expressing the receptor. More recently, CD30 has also become an attractive therapeutic target. The preliminary observations indicate that the methods currently used to detect CD30 expression, typically immunohistochemistry performed on formalin-fixed, paraffin-embedded tissues, may be suboptimal in regard to identifying CD30 as a therapeutic target since only a limited number of CD30 receptor molecules per cell may be sufficient to achieve therapeutic effect.

Brentuximab vedotin in CD30+ primary cutaneous T‐cell lymphomas: a review and analysis of existing data

“…Recent evidence shows immunohistochemical staining for CD30 positive cells may fail to demonstrate these cells even when they are present, and that both intra‐ and interlesional CD30 expression varies about 10% within the same patient. Hence, multiple biopsies from various lesions may be necessary to demonstrate expression . Additionally, some cases demonstrate response to BV even with very low or absent detection of CD30 on immunohistochemical analysis, suggesting that very few cell surface receptors are necessary for BV to adequately interact with the neoplastic cell …”

“…This value is slightly lower than reported figures in the two included Phase II trials but similar to previous reports. 20,22,28 Fatigue (36.9%) and nausea 29,30 Additionally, some cases demonstrate response to BV even with very low or absent detection of CD30 on immunohistochemical analysis, suggesting that very few cell surface receptors are necessary for BV to adequately interact with the neoplastic cell. 22,31 The main limitation of this study is that it is primarily descriptive; however, performing a meta-analysis would have yielded biased results due to the small sample sizes in the underpowered studies that were reviewed.…”

Multicentric MFI30 study: Standardization of flow cytometry analysis of CD30 expression in non‐Hodgkin lymphoma

“…ALCL is now well described in the WHO classification (Swerdlow, Campo, Harris, et al, 2017) as CD30‐positive T‐cell lymphoma. CD30 expression has also been reported in other subtypes of non‐Hodgkin's lymphoma (NHL); in approximately 30% of T‐cell lymphomas (Bisig et al, 2013; Falini et al, 1995) and in 15–20% of Diffuse Large B‐Cell Lymphomas (DLBCL), such as anaplastic variant, primary mediastinal large B‐cell lymphoma, and primary effusion lymphoma (PEL; de Leval & Gaulard, 2010; Higgins & Warnke, 1999; Piris, Brown, Gatter, & Mason, 1990; Wasik, Jimenez, & Weisenburger, 2013). Brentuximab Vedotin (BV) is a CD30 monoclonal Ab conjugated to the potent inhibitor of microtubule polymerization, monomethyl auristatin E (MMAE).…”

CD30 Expression and Its Correlation with Clinicopathologic Features in Indonesian Diffuse Large B-Cell Lymphoma

“…This lower result might reflect differences in underlying tumor biology from a diverse ethnic population [4-13-16]. CD30 expression assessment is closely related to pre-analytical phase including sample handling and IHC staining processes [21][22][23]. The pre-analytic process is most likely to give false positive or negative results [24][25].…”