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Table of Contents
Definition / general | Interpretation | Uses by pathologists | Microscopic (histologic) images | Positive staining - disease | Negative staining | Molecular / cytogenetics imagesCite this page: HER2. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/stainsher2.html. Accessed July 12th, 2017.
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
- 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-)
- Basal-like (ER-, HER2-, EGFR+ or cytokeratin 5/6+)
Interpretation
- 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
- 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
Microscopic (histologic) images
Images hosted on PathOut server:
Breast, neuroendocrine carcinoma, HER2-
Breast, Paget's disease
Images hosted on Other servers:
Bladder, carcinoma in situ, full thickness HER2+ staining vs dysplasia / reactive atypia
Breast, apocrine carcinoma
Breast, DCIS
HER-2 oncoprotein
Breast, ductal carcinoma vs medullary
Breast, Paget disease and underlying DCIS
Esophagus, adenocarcinoma
Stomach, gastric and gastroesophageal junction adenocarcinoma
Positive staining - disease
- 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)
- Paget 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
- 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 disease
Molecular / cytogenetics images
Breast, apocrine carcinoma - HER2+ by CISH
Esophagus, adenocarcinoma
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