Stains & CD markers

Editor-in-Chief: Debra L. Zynger, M.D.
Rong Xia, M.D., Ph.D.
Raavi Gupta, M.D.

Topic Completed: 25 July 2019

Minor changes: 25 June 2021

Copyright: 2019-2022,, Inc.

PubMed Search: EZH2[TI] review[ptyp]

Rong Xia, M.D., Ph.D.
Raavi Gupta, M.D.
Page views in 2021: 464
Page views in 2022 to date: 18
Cite this page: Xia R, Gupta R. EZH2. website. Accessed January 19th, 2022.
Definition / general
Essential features
  • Enhancer of zeste 2 polycomb repressive complex 2 subunit
  • Catalyzes the trimethylation of histone 3 lysine 27 (H3K27me3), associated with transcriptional repression
    • Further suppresses the activity of genes related to stem cell differentiation and ablates normal development (Nat Med 2016;22:128)
  • Gain of function mutations or overexpression is associated with non-Hodgkin lymphoma, squamous cell carcinoma, malignant liver neoplasm and melanoma (Clin Cancer Res 2011;17:2613)
  • Gain of function mutations or overexpression is associated with worse progression in prostate cancer, breast cancer, bladder cancer, endometrial cancer, myelodysplastic syndromes and melanoma (Nat Med 2016;22:128)
  • Loss of function mutations is associated with a subset of myelodysplastic syndromes / myeloproliferative neoplasms and T cell acute lymphoblastic leukemia (Nat Med 2016;22:128)
  • Potential therapeutic target; 2 phase II trials of EZH2 inhibitors for treating lymphoma are underway (Nat Med 2016;22:128)
Diagrams / tables

Images hosted on other servers:

EZH2 as a repressor

  • Nuclear staining
Uses by pathologists
  • Differentiate malignant effusions (MOC31 membranous and EZH2 nuclear staining) from benign effusions (Diagn Cytopathol 2017;45:118, Diagn Cytopathol 2014;42:111)
  • Differentiate malignant mesothelioma (loss of BAP1 and high expression of EZH2) from benign mesothelial proliferation (Histopathology 2017;70:722)
  • Differentiate squamous cell carcinoma (> 35% staining) from normal skin (< 5% stain) and actinic keratosis (< 15% staining) (Eur J Dermatol 2014;24:41)
  • Differentiate cholangiocarcinoma (positive) from ductular reaction and bile duct adenoma (negative) (Am J Surg Pathol 2014;38:364)
  • Differentiate invasive high grade urothelial carcinoma (high intensity and percentage in staining) of the bladder from noninvasive low grade urothelial carcinoma and carcinoma in situ (low intensity and percentage in staining) (Urol Oncol 2012;30:428)
  • Differentiate malignant (positive) and benign (negative) hepatic tumors (Diagn Pathol 2012;7:86)
Prognostic factors
Microscopic (histologic) description
  • Scattered nuclear staining in the basal layer of the benign epithelium in the gastrointestinal tract, bronchus, endometrium and skin
  • Increased intensity of staining and number of positive cells in invasive squamous cell carcinoma, adenocarcinoma of the colorectum, urothelial carcinoma, renal cell carcinoma, NK / T cell lymphoma and high grade neuroendocrine tumor
Microscopic (histologic) images

Contributed by Raavi Gupta, M.D.

Low grade neuroendocrine tumor

High grade neuroendocrine tumor

Normal skin

Squamous cell carcinoma in situ

Squamous cell carcinoma

Positive staining - normal
  • Testis, placenta, bone marrow: diffuse and strong staining
  • Skin: scattered and weak staining in the basal and spinous layer of the epidermis and strong intense stain in Langerhans cells (Eur J Dermatol 2014;24:41)
  • Esophagus, vagina, cervix: scanty and weak staining in the basal layer of the squamous epithelium
  • Gastrointestinal tract, fallopian tube, endometrium: scattered and weak staining in the basal layer of the epithelium and deep crypts
Positive staining - disease
Negative staining
Board review style question #1
A 56 year old woman complains of cough, fatigue and low fever for 3 months worsening in the past 2 days and is admitted to the emergency room. Chest Xray shows opacity in the right upper lobe and extensive effusion in the right lung. Thoracentesis reveals tan-yellow fluid containing scanty clusters of epithelioid cells forming 3 dimensional architecture, with slightly enlarged nuclei and prominent nucleoli in the background of extensive inflammation, neutrophil infiltration and degenerative changes. Which of the following immunostains support the diagnosis of a malignant effusion over a benign effusion in the cell block?

  1. MOC31 negative and EZH2 cytoplasmic staining
  2. MOC31 membranous and EZH2 nuclear staining
  3. MOC31 membranous and EZH2- staining
  4. MOC31 nuclear and EZH2 cytoplasmic staining
Board review style answer #1
B. MOC31 membranous and EZH2 nuclear staining support the diagnosis of malignant effusion over benign effusion.

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Reference: EZH2
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