E-cadherin

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Stains & CD markers
E-cadherin

Authors: Samuel Bidot, M.D., Xiaoxian (Bill) Li, M.D., Ph.D.

Editorial Board Member: Julie M. Jorns, M.D.

Editor-in-Chief: Debra L. Zynger, M.D.

Last author update: 15 February 2021

Last staff update: 3 October 2023

Copyright: 2002-2024, PathologyOutlines.com, Inc.

PubMed Search: E-cadherin

Table of Contents

Cite this page: Bidot S, Li X. E-cadherin. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsecadherin.html. Accessed December 21st, 2024.

Definition / general

E-cadherin is a transmembrane protein involved in cellular adhesion and polarity maintenance
E-cadherin is expressed in almost all epithelial cells
Loss of E-cadherin expression is associated with gain of tumor cell motility and invasiveness

Essential features

E-cadherin is a transmembrane protein involved in cellular adhesion
Expressed in almost all epithelial cells
Normal pattern of expression is membranous
Abnormal pattern is loss or decrease of membranous expression
Common use is to differentiate invasive and in situ / invasive lobular carcinoma (-) from in situ / invasive ductal carcinoma (+) of the breast

Terminology

Synonym: cadherin-1

Pathophysiology

Epithelial cadherin (E-cadherin) is a transmembrane protein (Histopathology 2016;68:57)
- Extracellular domain involved in intercellular adhesion and polarity maintenance
- Cytoplasmic domain attached to actin units α / γ / β- and p120 catenins
Encoded by CDH1 (CaDHerin-1) gene located on chromosome 16 (16q22.1)
Biallelic inactivation of CDH1 results in the loss of membranous expression of E-cadherin and gain of motility of tumor cells

Clinical features

Heterozygous germline alteration of the CDH1 gene is associated with hereditary diffuse gastric cancer syndrome and invasive lobular carcinoma of the breast (Prog Mol Biol Transl Sci 2013;116:337)

Interpretation

Normal pattern is strong circumferential membranous staining
Abnormal pattern is loss or decrease / attenuation of membranous staining
Uninvolved epithelial cells can be used as reference
- Useful in lobular neoplasia of the breast: staining is patchy, weak or complete loss compared with uninvolved luminal cells

Uses by pathologists

To distinguish lobular carcinoma in situ from ductal carcinoma in situ (Histopathology 2016;68:57)
- May be critical, as management could be different
- Only useful in challenging cases
- Morphology takes precedence over E-cadherin stain as aberrant protein expression may be present despite non-functional E-cadherin-catenin complex (Am J Surg Pathol 2008;32:773)
To distinguish invasive lobular from invasive ductal carcinoma
- Less critical, as treatment remains similar
- High grade invasive ductal carcinoma may have aberrant E-cadherin staining patterns
Others
- Other neoplasms with loss characterized by tumoral cell discohesion, typically:
  - Solid pseudopapillary neoplasm of the pancreas (-) versus other pancreatic neoplasms (+) (Arch Pathol Lab Med 2017;141:990)
  - Diffuse type gastric adenocarcinoma (Nat Med 2015;21:449)
  - Plasmacytoid urothelial carcinoma (Hum Pathol 2019;90:27)
- Hematopoietic malignancies of erythroid differentiation (+) (Am J Clin Pathol 2014;141:656)

Prognostic factors

Loss of E-cadherin is associated with tumor progression, chemoresistance and metastases (Cells 2020;9:428)

Microscopic (histologic) images

Contributed by Xiaoxian (Bill) Li, M.D., Ph.D.

Ductal carcinoma in situ with lobular features

Florid lobular carcinoma in situ

Invasive lobular carcinoma of the breast

Lobular carcinoma in situ

Virtual slides

Images hosted on other servers:

Pleomorphic lobular carcinoma

E-cadherin

Positive staining - normal

All normal epithelial cells except (Arch Histol Cytol 2006;69:135):
- Granulosa cells
- Adrenal gland
Hematopoietic erythroid precursors (Am J Clin Pathol 2014;141:656)

Positive staining - disease

Most carcinomas have strong and diffuse membranous staining
- Invasive and in situ ductal carcinoma of the breast (> 90%) (Histopathology 2016;68:57)
- Squamous cell carcinoma of the oral cavity (40%) (BMC Cancer 2014;14:395)
- Lung adenocarcinoma (60%) (Mod Pathol 2004;17:430)
- Lung squamous cell carcinoma (50%) (Mod Pathol 2004;17:430)
- Low grade urothelial papillary carcinoma (100%) (Hum Pathol 2015;46:1836)
- Gynecologic serous carcinoma (100%) (Mod Pathol 2008;21:1147)
- Colorectal carcinoma (85%) (Oncol Rep 2009;21:57)
- Hepatocellular carcinoma (60%) (J Pathol Transl Med 2016;50:327)
- Salivary gland tumors (100%) (Int J Surg Pathol 2006;14:212)
Immature erythroblasts, e.g. pure erythroid leukemia (Am J Hematol 2019;94:726)
Aberrant (nuclear) expression has been reported in (Adv Anat Pathol 2008;15:234):
- Solid pseudopapillary and neuroendocrine pancreatic neoplasms
- Merkel cell carcinoma
- Clear cell renal cell carcinoma

Negative staining

Carcinomas with loss of E-cadherin expression:
- Lobular carcinoma of the breast (Histopathology 2016;68:57)
- Diffuse type gastric cancer (30%) (J Clin Pathol 2010;63:635)
Pseudopapillary neoplasm of the pancreas (0%) (Hum Pathol 2008;39:251)
Plasmacytoid urothelial carcinoma (43%) (Hum Pathol 2019;90:27)

Board review style question #1

Cannot diagnose due to inconsistent H&E and E-cadherin staining pattern
DCIS with positive E-cadherin expression
Invasive ductal carcinoma
LCIS with decreased E-cadherin expression

Board review style answer #1

D. LCIS with decreased E-cadherin expression. The morphology shows typical features of lobular carcinoma in situ with eccentric nuclei and cytoplasmic mucin. E-cadherin stain shows decreased membranous expression, consistent with aberrant E-cadherin staining in LCIS.

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