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Testing Biomarkers in Gastroesophageal Adenocarcinoma (GEA)

There were ~1.6 million new cases of gastroesophageal cancers across the globe in 2018. This represents the seventh (esophageal) and fifth (stomach) most common cancers worldwide1

The frequency of overexpression of HER2 is slightly greater for cancers at the gastroesophageal junction in comparison to the stomach, and overexpression in the stomach varies by2:

  • Histologic type (more common in intestinal type than in diffuse type)2

  • Differentiation (more common in well and moderately differentiated tumors than in poorly differentiated tumors)2

Guideline-recommended sample preparation helps to improve test accuracy2

HER2 testing in gastroesophageal adenocarcinoma (GEA)

The CAP/ASCP/ASCO Guidelines strongly recommend HER2 testing in patients with gastroesophageal adenocarcinoma2

The HER2 oncogene is amplified and/or overexpressed in 7% to 38% of gastroesophageal adenocarcinoma cases2

Algorithm for HER2 testing in patients with gastroesophageal adenocarcinoma2

Chart displaying the algorithm for HER2 testing in patients with gastroesophageal adenocarcinoma

Image adapted from Bartley AN, et al. Arch Pathol Lab Med. 2016;140(12):1345-1363.

The guidelines for scoring IHC in gastroesophageal adenocarcinoma differ from those used in breast cancer2,3

  • In comparison with breast cancer, the heterogeneity of immunostaining is greater in gastroesophageal adenocarcinoma2

    • Gastroesophageal adenocarcinoma cells do not often present with the completeness of membrane staining that is required for positivity in breast cancer2

    • HER2 expression is often seen in a basolateral pattern in gastroesophageal adenocarcinoma2

  • The CAP/ASCP/ASCO guidelines and NCCN recommend the use of the Ruschoff/Hofmann method in scoring HER2 IHC and ISH results for gastroesophageal adenocarcinoma2,4

If IHC is used as a primary test platform, applying breast cancer principles and scoring criteria to gastroesophageal adenocarcinoma may result in a 50% false-negative rate3

Breast cancer

Breast cancer images provided by Leo A Niemeier, MD. Advanced GEA biopsy images provided by David G Hicks, MD, Bruce Horten, MD, and Christa Whitney-Miller, MD.

CAP/ASCP/ASCO guidelines recommend dual-probe in situ hybridization (ISH) be used to retest IHC 2+ (equivocal) samples2

The guidelines for scoring ISH differ from those used for breast cancer to compensate for the greater heterogeneity of GEA2

Guidelines for scoring ISH

ASCO=American Society of Clinical Oncology; ASCP=American Society for Clinical Pathology; CAP=College of American Pathologists; CEP17=chromosome enumeration probe 17; GEA=gastroesophageal carcinoma; HER2=human epidermal growth factor receptor 2; IHC=immunohistochemistry; NCCN=National Comprehensive Cancer Network

    • Worldwide cancer data. World Cancer Research Fund International. https://www.wcrf.org/dietandcancer/cancer-trends/worldwide-cancer-data. Accessed January 28, 2020.

      Worldwide cancer data. World Cancer Research Fund International. https://www.wcrf.org/dietandcancer/cancer-trends/worldwide-cancer-data. Accessed January 28, 2020.

    • Bartley AN, et al. HER2 testing and clinical decision making in gastroesophageal adenocarcinoma. Arch Pathol Lab Med. 2016;140(12):1345-1363.

      Bartley AN, et al. HER2 testing and clinical decision making in gastroesophageal adenocarcinoma. Arch Pathol Lab Med. 2016;140(12):1345-1363.

    • Rüschoff J, et al. HER2 diagnostics in gastric cancer—guideline validation and development of standardized immunohistochemical testing. Virchows Arch. 2010;457:299-307.

      Rüschoff J, et al. HER2 diagnostics in gastric cancer—guideline validation and development of standardized immunohistochemical testing. Virchows Arch. 2010;457:299-307.

    • Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Esophageal and Esophagogastric Junction Cancers V.3.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed December 10, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

      Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Esophageal and Esophagogastric Junction Cancers V.3.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed December 10, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

    • Genentech. Data on File. 2019.

      Genentech. Data on File. 2019.

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