Deviating HER2 test results in gastric cancer: analysis from the prospective multicenter VARIANZ study.
Esophago-gastric junction cancer
Gastric cancer
HER2 status
Immunohistochemistry
Survival
Trastuzumab
Journal
Journal of cancer research and clinical oncology
ISSN: 1432-1335
Titre abrégé: J Cancer Res Clin Oncol
Pays: Germany
ID NLM: 7902060
Informations de publication
Date de publication:
Mar 2023
Mar 2023
Historique:
received:
15
05
2022
accepted:
12
07
2022
pubmed:
28
8
2022
medline:
8
3
2023
entrez:
27
8
2022
Statut:
ppublish
Résumé
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. 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). 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). Tumor localization and histological subtype have an impact on HER2 test deviation rates. Assessment of HER2 remains challenging for GC and EGJC.
Identifiants
pubmed: 36030286
doi: 10.1007/s00432-022-04208-6
pii: 10.1007/s00432-022-04208-6
pmc: PMC9984518
doi:
Substances chimiques
Receptor, ErbB-2
EC 2.7.10.1
Trastuzumab
P188ANX8CK
Biomarkers, Tumor
0
Types de publication
Multicenter Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1319-1329Informations de copyright
© 2022. The Author(s).
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