Interim Analysis of Concordance Study of Immunohistochemical CD30 Expression Detected By Multiple Assays and the Ventana CD30 Assay in Chinese Lymphoma Patients (CREDIT Study)
Authors: Jiang Xiang-Nan , Xu Mei-Fang , Chen Lu-Shan , Meng Bin , Gong Wen-Chen , Sun Qi , Zhang Hong-Ju , Cai Mu-Yan , Duan Jin-Ling , Zhang Zhi-Hong , Gong Yu-Xi , Feng Xiao-Li , Xue Xue-Min , Zhang Cui-Juan , Lu Zhao-Hui , Jia Cong-Wei , Ao Qi-Lin , Kuang Dong , Guo Ling-Chuan , Tong Xing , Guo Zi-Heng , Han Miao , Li Xiao-Qiu 
Published: December 2024

Introduction:
Standardization of methods for the immunohistochemical detection of CD30 expression and improvement of its reproducibility is critical for determining patient eligibility for anti-CD30 therapy. The protocol of the VENTANA CD30 assay has been well-optimized based on a pilot study. The current study aims to evaluate the staining concordance of CD30 detected by nine alternative immunohistochemical (IHC) assays in addition to the VENTANA CD30 assay. This evaluation is pivotal for exploring more equivalent detection methods to assess CD30 expression in patients with malignant lymphomas.
Methods:
This multi-centre retrospective study aimed to enroll 700-1,000 patients diagnosed with malignant lymphomas from 17 institutes across China. Tissue sections were stained using the VENTANA CD30 assay or at least one of the nine IHC assays utilizing different antibodies (umAB256 (zsbio); Ber-H2 (Maixin); Ber-H2 (DAKO); JCM182 (Leica) and platforms (Ventana BenchMark; DAKO; Leica). The staining results were evaluated by a panel of three independent expert hematopathologists in China based on consensus criteria. The primary objective of the study was to evaluate the concordance of semiquantitative results of CD30 staining detected by nine IHC assays and the VENTANA CD30 assay. Consistency was assessed by the intraclass correlation coefficient (ICC). To observe the effect of CD30 expression level on the concordance of different assays, cases with high-level expression (such as cHL and ALCL) and with low-level expression (with positivity &lt;10% cells) were included in the subgroup analysis.
Results:
In this interim analysis, 346 patients from 12 institutes were enrolled, and 245 of whom met the inclusion criteria, after excluding those who met the exclusion and rejection criteria. With the exception of Ber-H2 (DAKO) + Ventana BenchMark assay, which showed a moderate concordance with the VENTANA CD30 assay, the concordance between the other eight CD30 IHC assays and the VENTANA CD30 assay was good or excellent, regardless whether cases with low-level expression were included. Excluding cases with high-level expression, the concordance between Ber-H2 (DAKO) + Ventana BenchMark assay and the VENTANA CD30 assay remained moderate, the same result got in Ber-H2(Maixin)+Ventana BenchMark. When excluding cases with low-level expression, the concordance of the umAB256 (zhongshanjinqiao) + Ventana BenchMark and Ber-H2 (Maixin) + Dako with the VENTANA CD30 assay turned to be moderate similarly.
Conclusions:
Overall, the concordance of nine CD30 IHC assays with the VENTANA CD30 assay varied from moderate to excellent, suggesting the reliability of the application of these approaches. Additional efforts are needed to optimize those assays with moderate concordance to inform treatment decisions better.