Gastric HER2 Biomarker Reporting
ToGA/Hofmann IHC scoring criteria for gastric/GEJ adenocarcinoma, with reflex-ISH guidance.
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Educational and decision-support tool only. Does not replace the current ASCO/CAP/ASCP guideline, institutional protocol, ISH/FISH testing where indicated, or professional pathologist judgment.
Reference
Different from breast HER2 scoring
Scores HER2 IHC using the ToGA trial criteria, modified from Hofmann et al. — the standard method for gastric/GEJ adenocarcinoma, distinct from breast HER2 scoring criteria.
As in breast, only membranous staining counts — cytoplasmic staining is not scored. Unlike breast, complete membranous staining is not required for positivity: basolateral or lateral membranous reactivity qualifies, reflecting the secretory nature of gastric epithelium.
Criteria differ meaningfully between specimen types — surgical specimens are scored by percentage of tumor cells; biopsies are scored by the presence of even one qualifying cell cluster, since biopsies capture only a small tissue fragment.
Criteria used in the ToGA trial for HER2 IHC scoring
Cancer cell cluster = ≥5 neoplastic cells.
| Score | Surgical specimen pattern | Biopsy specimen pattern | Assessment |
|---|---|---|---|
| 0 | No reactivity or membranous reactivity in <10% of cancer cells | No reactivity or no membranous reactivity in any cancer cell | Negative |
| 1+ | Faint or barely perceptible membranous reactivity in ≥10% of cancer cells; cells are reactive only in part of their membrane | Cancer cell cluster with a faint or barely perceptible membranous reactivity, irrespective of percentage of cancer cells positive | Negative |
| 2+ | Weak to moderate complete, basolateral, or lateral membranous reactivity in ≥10% of tumor cells | Cancer cell cluster with a weak to moderate complete, basolateral, or lateral membranous reactivity, irrespective of percentage of cancer cells positive | Equivocal |
| 3+ | Strong complete, basolateral, or lateral membranous reactivity in ≥10% of cancer cells | Cancer cell cluster with a strong complete, basolateral, or lateral membranous reactivity, irrespective of percentage of cancer cells positive | Positive |
Testing algorithm
Perform IHC testing first. If IHC is 2+ (equivocal), reflex to ISH (e.g., FISH). IHC 0/1+ (negative) or IHC 3+ (positive) do not require further ISH testing. The Ruschoff/Hofmann method is recommended for scoring both HER2 IHC and ISH results in gastroesophageal adenocarcinoma.
Sources
Hofmann M, Stoss O, Shi D, et al. Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology. 2008;52(7):797-805.
Bang YJ, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376(9742):687-697.
Bartley AN, Washington MK, Colasacco C, et al. HER2 Testing and Clinical Decision Making in Gastroesophageal Adenocarcinoma: Guideline From the College of American Pathologists, American Society for Clinical Pathology, and the American Society of Clinical Oncology. J Clin Oncol. 2017;35(4):446-464.
The table supplied for this app cited a numbered reference list that was not included in the excerpt provided when this app was built; the sources above are the well-established primary publications underlying the ToGA/Hofmann criteria and the current ASCO/CAP/ASCP testing guideline, not a reproduction of that specific unresolved reference list.