Stains & CD markers
Cytokeratin 5/6 and CK5

Editor-in-Chief: Debra L. Zynger, M.D.
Robert Terlević, M.D.
Semir Vranić, M.D., Ph.D.

Last author update: 3 June 2019
Last staff update: 20 October 2022 (update in progress)

Copyright: 2019-2023,, Inc.

PubMed Search: CK5/6 [title]

Robert Terlević, M.D.
Semir Vranić, M.D., Ph.D.
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Cite this page: Terlević R, Vranić S. Cytokeratin 5/6 and CK5. website. Accessed February 8th, 2023.
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)
  • K5, K6, keratin 5, keratin 6, basal cytokeratins, intermediate molecular weight cytokeratins
Clinical features
  • 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 Jijgee Munkhdelger, M.D., Ph.D., Andrey Bychkov, M.D., Ph.D. and Semir Vranić, M.D., Ph.D.
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Breast tubular adenoma immunoprofile

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Intraductal papilloma with DCIS immunoprofile

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Intraductal papilloma with DCIS, CK5/6

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Basal-like triple negative breast cancer

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Apocrine metaplasia of the breast

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Metastatic squamous cell carcinoma of the cervix

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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 style 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 style answer #1
Board review style 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 style answer #2
D. In situ high grade urothelial carcinoma versus T2 high grade urothelial carcinoma

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