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Stains

HER2

Reviewer: Nat Pernick, M.D. (see Reviewers page)
Revised: 24 December 2012, last major update December 2012
Copyright: (c) 2002-2012, PathologyOutlines.com, Inc.

See also Breast malignant chapter

General
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● 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
● DNA microarray profiling studies have divided invasive breast carcinoma into molecular subtypes: luminal A (ER+, HER2-), luminal B (ER+, HER2+), HER2 positive (ER-, HER2+), normal breast-like (ER+, PR+, HER2-) and basal-like (ER-, HER2-, EGFR+ or cytokeratin 5/6+)

Interpretation
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● HER2 testing valid on breast specimens fixed in fomalin up to 96 hours (Am J Clin Pathol 2012;137:691), but not accurate with Bouin fixative (Am J Clin Pathol 2011;136:754)
● For GI specimens, results vary by type of HER2 antibody used (Am J Clin Pathol. 2012;137:583)
● HER2 IHC analysis for breast cancer performed by image analysis can produce accurate results (Am J Clin Pathol 2012;137:270)
● Can perform IHC and ISH on single slide (Am J Clin Pathol 2012;137:102, Am J Clin Pathol. 2012;138:837)
● For interpretation and images with breast cancer, see Breast malignant chapter

Uses by pathologists
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● Breast cancer: confirm histologic classification (based on molecular classification), determine use of anti-HER2 therapies including Herceptin and Tykerb, negative prognostic factor
● Gastric and gastroesophageal junction adenocarcinoma: determine use of anti-HER2 therapies (Arch Pathol Lab Med 2012;136:691), which improve survival in HER2+ patients

Micro images
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Bladder: carcinoma in situ has full thickness HER2+ staining versus dysplasia and reactive atypia


Bladder: micropapillary carcinoma

● See Breast malignant chapter for extensive collection of breast related images


Breast: apocrine carcinoma - HER2+ by immunohistochemistry (HER2+ in 1/3)

   
Breast: DCIS

 
Breast: ductal carcinoma (invasive) in male patient (left: HER2+, right: HER2-)


Breast: ductal carcinoma (HER2+) versus medullary carcinoma (HER2-)


Breast: neuroendocrine carcinoma (HER2-)

   
Breast: Paget's disease and underlying DCIS

 
Esophagus: adenocarcinoma


Neuroblastic tumors (note: HER2 by IHC is NOT accompanied by gene amplification)


Skin: apocrine hidrocytoma and nodular hidradenoma are HER2+

   
Stomach: gastric and gastroesophageal junction adenocarcinoma

Positive staining - disease
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● Bladder: high grade papillary urothelial carcinoma (noninvasive), micropapillary carcinoma (Mod Pathol 2011;24:1111), urothelial carcinoma in situ (full thickness HER2+, Am J Clin Pathol 2011;136:881)
● Breast: apocrine carcinoma (30%), apocrine DCIS (47%), ductal carcinoma (20%), DCIS (15-30%), inflammatory carcinoma (50%), lipid-rich carcinoma (71%+, Tumori 2008;94:342, Ann Diagn Pathol 2011;15:225), lobular carcinoma-pleomorphic variant, micropapillary (95%), mucinous cystadenocarcinoma (Hum Pathol 2010;41:910), oncocytic, Paget's disease
● Esophagus: adenocarcinoma (29%, Mod Pathol 2011;24:908)
● Lung: adenocarcinoma (10-12%, Mod Pathol 2012;25:1566)
● Neuroblastic tumors: HER2 staining is NOT accompanied by gene amplification (Mod Pathol 2010;23:1261)
● Skin: apocrine hidrocytoma and nodular hidradenoma (Mod Pathol 2004;1:28)
● Stomach: adenocarcinomas (5-15% intestinal type, < 1% diffuse type)
● Uterus: serous carcinoma (18-61%)

Negative staining
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● Breast myoepithelial and Toker cells
● Breast: adenoid cystic carcinoma, lobular carcinoma, triple negative carcinomas [basal-like, medullary (Arch Pathol Lab Med 2003;127:1458), metaplastic, squamous]
● Skin: Bowen's disease

Molecular images
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Bladder: micropapillary carcinoma

 
Breast: apocrine carcinoma - HER2+ by CISH


Esophagus: adenocarcinoma

End of Stains > HER2

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