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
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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
Image adapted from Bartley AN, et al. Arch
Pathol Lab Med. 2016 Dec;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 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
GEA=gastroesophageal carcinoma; ASCO=American
Society of Clinical Oncology; ASCP=American Society for Clinical
Pathology; CAP=College of American Pathologists; CEP17=chromosome
enumeration probe 17; HER2=human epidermal growth factor receptor 2;
IHC=immunohistochemistry; NBF=neutral buffered formalin.
References
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Click - to close
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.
Rüschoff J, et al. HER2 diagnostics in gastric cancer—guideline
validation and development of standardized immunohistochemical
testing. Virchows Arch. 2010;457:299-307.
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