Deviating HER2 test results in gastric cancer: analysis from the prospective multicenter VARIANZ study
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Published:2022-08-27
Issue:3
Volume:149
Page:1319-1329
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ISSN:0171-5216
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Container-title:Journal of Cancer Research and Clinical Oncology
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language:en
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Short-container-title:J Cancer Res Clin Oncol
Author:
Kolbe KatharinaORCID, Haffner IvonneORCID, Schierle KatrinORCID, Maier Dieter, Geier Birgitta, Luber BirgitORCID, Bläker Hendrik, Wittekind Christian, Lordick FlorianORCID
Abstract
Abstract
Purpose
The prospective multicenter VARIANZ study aimed to identify resistance biomarkers for HER2-targeted treatment in advanced gastric and esophago-gastric junction cancer (GC, EGJC). HER2 test deviations were found in 90 (22.3%) of 404 cases (central versus local testing) and were associated with negative impact on survival for trastuzumab-treated patients. Here, we investigated methodological and biological variables that may promote deviating HER2 test results.
Methods
We analyzed HER2 testing procedures and participation in quality assurance programs of 105 participating local pathology laboratories. Furthermore, tumor localization and histological subtypes were compared between patients with centrally confirmed (central HER2 + /local HER2 + , n = 68) and unconfirmed HER2 status (central HER2 −/local HER2 + , n = 68).
Results
For central HER2 testing, concordance between in situ hybridization (ISH) and immunohistochemistry (IHC) was 98.3%, with IHC sensitivity of 93.3% (84 IHC + of 90 ISH +), specificity of 99.5% (389 IHC- of 391 ISH-), and a positive diagnosis rate of 97.7%. Central confirmation of the local HER2 IHC scores were seen for the majority of locally HER2- IHC 0/1 (172/178; 96.6%), but less frequently for locally IHC3 + (57/124; 46.0%) cases. Deviation rate was not associated with IHC antibody platform used in the local pathology institute neither with participation in quality-assuring tests. Regarding tumor characteristics, deviating test results were more frequently found in GC vs. EGJC (69.1% vs. 39.7%; p = 0.001) and in Laurén diffuse vs. intestinal subtype (23.5% vs. 5.9%, p = 0.004).
Conclusion
Tumor localization and histological subtype have an impact on HER2 test deviation rates. Assessment of HER2 remains challenging for GC and EGJC.
Funder
Universitätsklinikum Leipzig
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology,General Medicine
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