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Optimizing assessment of CD30 expression in Hodgkin lymphoma by controlling for low expression
Shoib Sarwar1, Margaret E Tome1,2, Dean Billheimer3
1Department of Pathology, University of Arizona, Tucson, AZ, USA.
Insights
Standardizing CD30 staining methods is crucial for accurately assessing lymphomas. This study highlights the need for controls to detect low CD30 expression, improving patient stratification for therapies like brentuximab vedotin.
Area of Science:
- Oncology
- Immunohistochemistry
- Hematopathology
Background:
- Brentuximab vedotin (BV) is approved for CD30-expressing lymphomas.
- Accurate CD30 assessment is vital for clinical management.
- Discrepancies in BV response suggest issues with CD30 detection.
Purpose of the Study:
- To evaluate CD30 expression in classical Hodgkin lymphoma (CHL) and nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL).
- To assess a novel staining protocol for detecting low CD30 levels.
- To investigate intra-patient heterogeneity in CD30 expression.
Main Methods:
- Examined 29 CHL and 4 NLPHL cases.
- Utilized a staining protocol designed for low CD30 detection.
- Employed an evaluation system similar to the Allred scoring system.
Main Results:
- 10% of CHL cases showed low CD30 scores; 3% were negative.
- Three CHL cases exhibited very weak CD30 staining.
- One NLPHL case unexpectedly tested positive for CD30.
- Intra-patient heterogeneity in CD30 expression was observed.
Conclusions:
- Standardization of CD30 immunohistochemistry is essential.
- Using controls for low expression can prevent missed diagnoses.
- Improved CD30 assessment aids therapeutic stratification for lymphoma patients.
Abstract:
Since the approval of brentuximab vedotin (BV), assessment of CD30 status by immunohistochemistry gained increasing importance in the clinical management of patients diagnosed with CD30-expressing lymphomas, including classical Hodgkin lymphoma (CHL). Paradoxically, patients with low or no CD30 expression respond to BV. This discrepancy may be due to lack of standardization in CD30 staining methods. In this study, we examined 29 cases of CHL and 4 cases of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) for CD30 expression using a staining protocol that was designed to detect low CD30 expression levels, and an evaluation system similar to the Allred scoring system used for breast cancer evaluation. For CHL, 10% of cases had low scores and 3% were CD30 negative, with 3 cases in which the majority of tumor cells showed very weak staining. Unexpectedly, one of four cases of NLPHL was positive. We demonstrate intra-patient heterogeneity in CD30 expression levels and staining patterns in tumor cells. Three CHL cases with weak staining may have been missed without the use of control tissue for low expression. Thus, standardization of CD30 immunohistochemical staining with use of known low-expressing controls may aid in proper CD30 assessment and subsequent therapeutic stratification of patients.

