Concordance of laboratory assays for claudin 18.2 in gastric cancer tissue samples: independent proficiency testing and a descriptive non-interventional study.

Biomarker testing is vital for personalized cancer treatment with improved efficacy based on genotype and biomarker expression. This prospective, in vitro, non-interventional study accompanied an independent proficiency test to descriptively analyze the results of immunohistochemical claudin 18.2 (CLDN18.2) testing in gastric cancer tissue samples by laboratories in Germany, Austria, and Switzerland, using assays independently established in their institutions. CLDN18.2 is a biomarker and drug target for locally advanced unresectable/metastatic gastric and pancreatic cancer. During an open proficiency test (OPT), laboratories were provided with 10 gastric cancer tissue samples (cases) for staining, interpretation, and scoring by a pathologist. Results were submitted with stained tumor cell percentage and a binary CLDN18.2-positive/negative result for each sample (cut-off: ≥ 75% of tumor cells expressing membranous CLDN18 with ≥ 2+ [moderate to strong] staining intensity). Successful participation was defined as ≥ 90% of cases evaluated correctly. Overall proficiency of the OPT was acceptable if ≥ 80% of laboratories participated successfully. Fifty-four institutes registered for the OPT, and one resigned. Forty-two of 53 (79.2%) institutes participated successfully. The main source of errors was false negative results (false negative rate, 12%; false positive rate, 1%). Overall accuracy was 91%. The CLDN18 (43-14A) clone was used most frequently, with optimal staining results and minor interpretation problems observed. Two antibodies were associated with false negative results (ZR451 [Zeta/Zytomed]; EPR19202 [Abcam]). Staining quality was the major factor for successful analysis; interpretation errors were not significant. Ongoing quality assurance will enable establishment of appropriate staining protocols and accurate CLDN18.2 interpretation, thereby facilitating individually optimized treatment.