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Virchows Arch. 2019 May;474(5):551-560. doi: 10.1007/s00428-019-02541-9. Epub 2019 Mar 2.

HER2 testing in gastric cancer diagnosis: insights on variables influencing HER2-positivity from a large, multicenter, observational study in Germany.

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Institut für Pathologie, Universitätsklinikum Carl Gustav Carus an der Technischen Universität, Fetscherstraße 74, 01307, Dresden, Germany.
Institut für Pathologie, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.
Pathologische Institut, Universitätsklinik Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
Pathologisches Institut Mannheim, Medizinische Fakultät Mannheim der Universität Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
Interdisziplinären Tumorzentrum, Universitätsmedizin Mannheim, Theodor-Kutzer Ufer 1-3, 68167, Mannheim, Germany.
Thüringen-Kliniken "Georgius Agricola" GmbH, Rainweg 68, 07318, Saalfeld/Saale, Germany.
Zentrum für ambulante Medizin, Uniklinikum Jena gGmbH, Carl-Zeiss-Platz 8, 07743, Jena, Germany.
BDS Koch, Bibienastraße 5, 68723, Schwetzingen, Germany.
Roche Pharma AG, Emil-Barell-Straße 1, 79639, Grenzach-Wyhlen, Germany.
Institut für Pathologie Nordhessen and Targos Molecular Pathology GmbH, Germaniastr 7, 34119, Kassel, Germany.


HER2 testing in metastatic gastric or gastroesophageal junction cancer (mGC/mGEJC) is standard practice. Variations in HER2-positivity rates suggest factors affecting test quality; however, the influence of patient-, tumor-, and laboratory-related factors on HER2-positivity rates remains unknown. This observational, prospective study collected routine HER2 testing data from 50 pathology centers in Germany (January 2013-December 2015). For each sample, HER2 status, primary tumor location, method of sample retrieval, and other patient- and tumor-related parameters were recorded. A model for predicting the probability of HER2-positivity was developed using stepwise multiple logistic regression to identify influencing factors. Documented positivity rates and corresponding predicted HER2-positivity probabilities were compared to identify institutes with deviations in HER2-positivity. Data from 2761 mGC/mGEJC routine diagnostic specimens included 2033 with HER2 test results (1554 mGC, 479 mGEJC); overall HER2-positivity rates across centers were 19.8% and 30.5%, respectively. HER2-positivity correlated most with Lauren classification, then HER2 testing rate, primary tumor location, sample type, and testing method (all p < 0.05). Three institutes had model-predicted HER2-positivity rates outside the 95% confidence interval of their documented rate, which could not be explained by sample and center characteristics. Results demonstrated the high quality of routine HER2 testing in the mGC/mGEJC cohort analyzed. This is the first study investigating parameters impacting on HER2-positivity rates in mGC/mGEJC in routine practice and suggests that assessment of HER2 testing quality should consider primary tumor location, testing method and rate, and tumor characteristics. Accurate identification of patients with HER2-positive mGC/mGEJC is essential for appropriate use of HER2-targeted therapies.


Gastric cancer; Gastroesophageal junction cancer; HER2 testing; HER2-positivity; Statistical model

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