Stains
Cytokeratin 5/6


Topic Completed: 3 June 2019

Revised: 3 June 2019

Copyright: 2019, PathologyOutlines.com, Inc.

PubMed Search: ck5/6 [title]

Robert Terlević, M.D.
Semir Vranić, M.D., Ph.D.
Page views in 2019 to date: 9,257
Cite this page: Terlević R Cytokeratin 5/6. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/stainsck5and6.html. Accessed October 22nd, 2019.
Definition / general
  • Basic (type II) cytokeratins of molecular weight 58 kDa (CK5) and 56 kDa (CK6) (Cell 1982;31:11)
  • Common antibodies are directed against both cytokeratin 5 and 6
  • Major partner of CK5 is CK14, while CK6 pairs with CK16/17 (Exp Cell Res 2007;313:2244, Eur J Cell Biol 2004;83:735)
  • CK5 also detected by antibodies against high molecular weight cytokeratins (such as 34βE12, also known as K903) and pan-CK markers (such as CK AE1/AE3)
Essential features
  • Stains basal cells of prostate and basal / myoepithelial cells of breast and is used to rule out invasion
  • Useful for detecting benign breast proliferations (mosaic-like pattern) versus ductal carcinoma in situ (DCIS) (negative or rarely diffusely positive) (Pathology 2009;41:68)
  • Together with p63, used to detect squamous cell origin in poorly differentiated carcinomas (Am J Clin Pathol 2001;116:823)
Terminology
  • K5, K6, keratin 5, keratin 6, basal cytokeratins, intermediate molecular weight cytokeratins
Pathophysiology
Clinical features
Interpretation
  • CK5 and CK5/6: diffuse cytoplasmic staining with perinuclear enhancement
Uses by pathologists
  • Identify breast basal / myoepithelial cells and prostate basal cells
  • Distinguish breast usual ductal hyperplasia (UDH) and papillary lesions (mosaic-like pattern) from DCIS (usually negative, rarely diffusely positive) (Pathology 2009;41:68)
  • Distinguish epithelioid mesothelioma (CK5/6+ in 83%) from lung adenocarcinoma (CK5/6- in 85%) (Histopathology 2006;48:223), including in pleural effusions (CK5/6+ in 90% mesothelioma, 0% adenocarcinoma) (Diagn Cytopathol 2006;34:801)
  • Distinguish cutaneous spindle squamous cell carcinoma (CK5/6+ in 100%) from superficial epithelioid sarcoma (rare focal positivity) (J Cutan Pathol 2003;30:114)
  • Together with p63+, identify squamous origin in poorly differentiated metastatic carcinomas (e.g., cervical) (Am J Clin Pathol 2001;116:823)
  • CK5 preferred to K903 in antibody cocktails to rule out prostate carcinoma (Diagn Pathol 2012;7:81)
  • As part of panel to discriminate between undifferentiated sinonasal carcinoma (CK5/6-) and other poorly differentiated head and neck tumors (poorly differentiated squamous cell carcinoma, olfactory neuroblastoma and nasopharyngeal carcinoma) (Ann Diagn Pathol 2014;18:261)
  • CK5 used as part of panel to distinguish cutaneous metastasis of breast cancer from sweat gland carcinoma (Arch Pathol Lab Med 2011;135:975)
Prognostic factors
Microscopic (histologic) images

Contributed by Semir Vranić, M.D., Ph.D.
Missing Image Missing Image

Basal-like triple negative breast cancer

Missing Image Missing Image

Apocrine metaplasia of the breast


Missing Image Missing Image

Metastatic squamous cell carcinoma of the cervix

Missing Image Missing Image

Apocrine carcinoma of the breast



Contributed by Leica Microsystems, Biosystems Division

Mesothelioma CK5
(XM26) with intense
cytoplasmic and
membranous staining

Positive staining - normal
Positive staining - disease
Negative staining
  • Adenocarcinoma (colon, stomach), renal cell carcinoma, germ cell tumors, thyroid carcinomas, neuroendocrine carcinoma (lung, skin and gastrointestinal), epithelioid sarcoma, synovial sarcoma (Mod Pathol 2002;15:6)
  • Benign epithelial breast lesions other than UDH and papillary lesions: apocrine metaplasia and columnar cell change (Am J Surg Pathol 2005;29:734)
  • Sinonasal undifferentiated carcinoma (Ann Diagn Pathol 2014;18:261)
  • Well differentiated neuroendocrine tumors of skin (100%) (J Cutan Pathol 2017;44:557)
Board review question #1
    Which of the following immunohistochemical stains is specific for basal cells of stratified epithelia?

  1. CKAE1/AE3
  2. CD5
  3. CK5/6
  4. CK7
  5. K903
Board review answer #1
C. CK5/6

Reference: Cytokeratin 5/6

Comment Here
Board review question #2
    Which of the following differential diagnoses cannot be solved with a basal cell stain (such as CK5/6)?

  1. Breast usual ductal hyperplasia versus ductal carcinoma in situ
  2. Cribriform high grade prostatic intraepithelial neoplasia versus prostatic adenocarcinoma Gleason pattern 4
  3. Metastatic undifferentiated squamous cell carcinoma versus epithelioid sarcoma
  4. In situ high grade urothelial carcinoma versus T2 high grade urothelial carcinoma
  5. Basal-like triple negative breast carcinoma versus breast ductal carcinoma, NOS
Board review answer #2
D. In situ high grade urothelial carcinoma versus T2 high grade urothelial carcinoma

Reference: Cytokeratin 5/6

Comment Here
Back to top