Stains & CD markers
Cytokeratin 5/6 and CK5

Editorial Board Member: Brandon Umphress, M.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Robert Terlević, M.D.
Semir Vranić, M.D., Ph.D.

Last author update: 9 June 2023
Last staff update: 9 June 2023

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PubMed Search: CK5/6

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 May 19th, 2024.
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 is also detected by antibodies against high molecular weight cytokeratins (such as 34 beta E12, 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 (can be 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
  • 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%), including in pleural effusions (CK5/6+ in 90% mesothelioma, 0% adenocarcinoma) (Histopathology 2006;48:223, 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 for the detection of 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)
  • CK5/6 full thickness positivity specific for bladder condyloma acuminatum versus basal / patchy staining in papillary noninvasive urothelial carcinoma (Int J Surg Pathol 2022;30:260)
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

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Complex sclerosing lesion of the breast

Positive staining - normal
Positive staining - disease
Negative staining
Sample pathology report
  • Breast, core biopsy:
    • Benign breast tissue with usual ductal hyperplasia (see comment)
    • Comment: Sections show mildly distended breast gland lumina filled with a mixed population of cells showing a mosaic pattern expression of CK5/6, consistent with usual ductal hyperplasia.
Board review style question #1

    Which of the following is an important use of the CK5/6 immunostain?

  1. Confirm a diagnosis of epithelioid sarcoma
  2. Confirm a diagnosis of well differentiated neuroendocrine tumors of skin
  3. Identify a basal-like subtype of triple negative breast carcinoma (TNBC) with poorer prognosis
  4. Identify sinonasal undifferentiated carcinoma
Board review style answer #1
C. Identify a basal-like subtype of triple negative breast carcinoma with poorer prognosis (shown in the image above). Answers A, B and D are incorrect because CK5/6 is typically negative in epithelioid sarcoma, well differentiated neuroendocrine tumors of skin and sinonasal undifferentiated carcinoma.

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Reference: Cytokeratin 5/6 and CK5
Board review style question #2
    What is the typical immunohistochemical staining pattern in usual ductal hyperplasia?

  1. Diffuse CK5 negativity
  2. Diffuse CK5 positivity
  3. Diffuse ER negativity
  4. Diffuse ER positivity
  5. Mosaic pattern CK5
Board review style answer #2
E. Mosaic pattern CK5. Mosaic pattern of CK5 refers to partial staining of the intraductal myoepithelial cell population. Answers A, B, C and D are incorrect because diffusely negative or positive CK5 or ER would indicate a clonal (neoplastic epithelial) cell population. Rarely, a neoplastic cell population can be CK5 positive, therefore use of a panel (CK5, p63, ER) is usually recommended.

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Reference: Cytokeratin 5/6 and CK5
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