Stains & molecular markers
HER2 nonbreast


Topic Completed: 1 December 2012

Revised: 30 December 2019

Copyright: 2002-2019, PathologyOutlines.com, Inc.

PubMed Search: HER2 [title]

Nat Pernick, M.D.
Y. Albert Yeh, M.D., Ph.D.
Page views in 2019: 4,035
Page views in 2020 to date: 758
Cite this page: Pernick N, Yeh YA. HER2 nonbreast. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/stainsher2.html. Accessed April 8th, 2020.
Definition / general
  • Also called Human Epidermal growth factor Receptor 2, c-erbB2, neu, ERBB2 and CD340
  • HER2 gene encodes transmembrane glycoprotein (p185) with tyrosine kinase activity
  • Related to EGFR
  • May cross reactive with P glycoprotein / CD243
  • Receptor acts via homo or heterodimerization with other EGFR family receptors
  • In embryogenesis, helps establish several cell lineages through mesenchyme-epithelial-neuroectodermal inductive processes
  • Influences cellular migration, differentiation, and interactions between cells
Diagrams / tables

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HER2 IHC
testing in gastric &
gastroesophageal
adenocarcinoma

Interpretation
Uses by pathologists
  • Gastric and gastroesophageal junction adenocarcinoma: determine use of anti-HER2 therapies (Arch Pathol Lab Med 2012;136:691), which improve survival in HER2+ patients
  • HER2 immunohistochemistry testing in gastric and gastroesophageal adenocarcinoma (see Diagrams / tables):
    • 2017 CAP / ASCP / ASCO guidelines (J Clin Oncol 2017;35:446, Virchows Arch 2010;457:299):
      • Representative surgical samples or at least 6 to 8 biopsy samples
      • Score 0: negative
        • No membranous staining or staining in < 10% of tumor cells (surgical specimen) or < 5 cohesive tumor cells (biopsy)
      • Score 1+: negative
        • Weak staining in only one part of the membrane in ≥ 10% of tumor cells (surgical specimen) or at least 5 cohesive tumor cells (biopsy)
      • Score 2+: equivocal, perform HER2 ISH
        • Moderate / weak complete or basolateral membranous staining in ≥ 10% of tumor cells (surgical specimen) or at least 5 cohesive tumor cells (biopsy)
      • Score 3+: positive
        • Strong or complete or basolateral membranous staining in ≥ 10% of tumor cells (surgical specimen) or at least 5 cohesive tumor cells (biopsy)
  • HER2 ISH in gastric and gastroesophageal adenocarcinoma (Mod Pathol 2012;25:637):
    • Positive: HER2/CEP17 ratio ≥ 2.0
    • Positive: HER2 copy number > 6.0 (using single probe)
    • HER2 copy number 4 to 6: use dual probe testing and recount 20 cells
Microscopic (histologic) images

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Bladder,
carcinoma in situ,
full thickness
HER2+ staining

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HER2 oncoprotein

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Esophagus, adenocarcinoma

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Stomach, gastric and gastroesophageal junction adenocarcinoma



Positive staining - disease
Negative staining
  • Skin: Bowen disease
Molecular / cytogenetics images

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Esophagus, adenocarcinoma

Board review style question #1
Which of the following results is interpreted as positive staining (score 3+) for HER2 in gastric and gastroesophageal adenocarcinoma?

  1. Intense nuclear and cytoplasmic staining > 10% of tumor cells
  2. Intense luminal membranous staining > 10% of tumor cells
  3. Intense basolateral membranous staining > 10% of tumor cells
  4. Intense luminal and lateral membranous staining > 10% of tumor cells
Board review answer #1
C. Intense basolateral membrane staining > 10% of tumor cells

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Reference: HER2 nonbreast
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