Stains & CD markers
Cytokeratins - uncommon
Copyright: 2003-2024, PathologyOutlines.com, Inc.
PubMed Search: CK1[title], CK2[title], CK3[title], CK4[title], CK9, CK11, CK13[title], CK15, CK16, KL-1
Cytokeratins - uncommon
Author: Nat Pernick, M.D.
Last author update: 1 October 2013
Last staff update: 25 June 2021
Copyright: 2003-2024, PathologyOutlines.com, Inc.
PubMed Search: CK1[title], CK2[title], CK3[title], CK4[title], CK9, CK11, CK13[title], CK15, CK16, KL-1
Table of Contents
Cytokeratin 1 (CK1) | Cytokeratin 2 (CK2) | Cytokeratin 3 (CK3) | Cytokeratin 4 (CK4) | Cytokeratin 9 (CK9) | Cytokeratin 11 (CK11) | Cytokeratin 13 (CK13) | Cytokeratin 15 (CK15) | Cytokeratin 16 (CK16) | Cytokeratin KL-1 | Microscopic (histologic) imagesCite this page: Pernick N. Cytokeratins - uncommon. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsck1.html. Accessed April 16th, 2024.
Cytokeratin 1 (CK1)
- Highest molecular weight keratin (67 - 68 kDa)
- Produced by KRT1 gene in complex manner (PLoS Genet 2006;2:e93)
- Associates with CK10
- Keratin 1b is expressed in eccrine sweat glands (J Invest Dermatol 2005;125:428)
- Reduced expression in HPV infection (Cancer Res 1990;50:3709)
- Mutations are associated with:
- Epidermolytic hyperkeratosis / bullous congenital ichthyosiform erythroderma (Dermatol Online J 2006;12:6)
- Greither’s syndrome (J Am Acad Dermatol 2005;53:S225)
- Striate palmoplantar keratoderma (J Invest Dermatol 2002;118:838)
- No significant clinical use by pathologists
- Positive staining - normal: endothelial cells, skin and other squamous epithelium (suprabasal spinous and granular layers), thymic Hassal’s corpuscle
- Positive staining - disease: angiosarcoma (73%), epithelioid hemangioendothelioma (100%), epithelioid sarcoma (70%), hemangioma (often), schwannoma (62%), squamous cell carcinomas (keratinizing), synovial sarcoma (28%), vascular tumors (greater in well versus poorly differentiated tumors)
- References: Hum Pathol 2001;32:873, OMIM 139350
Cytokeratin 2 (CK2)
- Molecular weight (CK2e) is 65.5 - 65.8 kDa
- Associates with CK10
- Mutations cause ichthyosis bullosa of Siemens (Br J Dermatol 2005;152:1353)
- K2e (epidermis) and K2p (palate) are encoded by separate genes, with < 75% identity at primary structural level; thus, are not true isoforms, although they cannot be distinguished by conventional 2D electrophoresis
- Uses by pathologists: no significant clinical use by pathologists
- Positive staining - normal: skin (upper spinous and granular cells) (Br J Dermatol 1999;140:582)
- References: OMIM 600194, Exp Cell Res 1992;202:132
Cytokeratin 3 (CK3)
- Molecular weight is 64 - 65 kDa
- Associates with CK12
- Mutations in KRT3 gene may cause Meesmann corneal dystrophy (Cornea 2005;24:928)
- Uses by pathologists: no significant clinical use by pathologists
- Positive staining - normal: corneal epithelium (full thickness), limbus epithelium (suprabasal)
- Negative staining: conjunctival epithelium
- Reference: OMIM 148043
Cytokeratin 4 (CK4)
- Molecular weight is 59 kDa
- Associates with CK13
- Downregulated in head and neck squamous cell carcinoma (Acta Otolaryngol 2006;126:967)
- Uses by pathologists: no significant clinical use by pathologists
- Case report: young man with novel mutation in the keratin 4 gene causing white sponge naevus (Br J Dermatol 2003;148:1125)
- Positive staining - normal: suprabasal cells of nonkeratinized stratified squamous epithelium of esophagus and cornea; also anus, larynx, pharynx, tongue (J Biol Chem 1998;273:23912)
- Reference: OMIM 123940
Cytokeratin 9 (CK9)
- Molecular weight of 64 kDa
- Partner may be CK1
- Regulated by dermal fibroblasts (J Invest Dermatol 1999;112:483)
- Mutations cause epidermolytic palmoplantar keratoderma (J Invest Dermatol 1998;111:1207)
- Uses by pathologists: no significant clinical use by pathologists
- Positive staining - normal: suprabasal epidermis of palms and soles, spermatogenic cells (J Invest Dermatol 1999;112:483, Mol Reprod Dev 2002;61:1)
- References: OMIM 607606, Wikipedia
Cytokeratin 11 (CK11)
Cytokeratin 13 (CK13)
- Molecular weight is 53 kDa
- Pairs with CK4
- Marker of mature but nonkeratinized squamous epithelium
- Downregulated in squamous cell carcinoma of head and neck and other sites (Oral Oncol 2005;41:183, Virchows Arch A Pathol Anat Histopathol 1991;418:249)
- Sensitive marker for retinoid bioactivity in skin warts of renal transplant recipients (Arch Dermatol 2002;138:61)
- Mutation causes familial white sponge nevus (J Dent Res 2001;80:919)
- Cable piliated Burkholderia cepacia binds to cytokeratin 13 of epithelial cells (Infect Immun 2000;68:1787)
- Uses by pathologists: no significant clinical use by pathologists
- Positive staining - normal: suprabasal layers of noncornified stratified epithelium, including squamous (nonkeratinized) epithelia of cervix, esophagus, larynx, oral cavity, tonsils, urothelium and respiratory type epithelium; may be filled with mucoid material or foamy macrophages
- Positive staining - disease: Brenner tumor; squamous metaplasia; squamous cell carcinoma (10%); urothelial carcinoma (well differentiated)
- Negative staining: epidermis
- References: J Dent Res 2001;80:919, OMIM 148065
Cytokeratin 15 (CK15)
- Molecular weight of 50 kDa
- Downregulated in activated keratinocytes in psoriasis, hypertrophic scars and skin injury (J Invest Dermatol 1999;112:362, Exp Cell Res 2000;254:80)
- Uses by pathologists: no significant clinical use by pathologists
- Positive staining - normal:
- Conjunctiva (basal cells) and cornea limbus epithelial cells (basal and suprabasal cells) (Invest Ophthalmol Vis Sci 2006;47:4780)
- Esophagus (Mol Cell Biol 2004;24:3168)
- Fetal epidermis and nail, hair follicle bulge and follicular stem cells (Clin Exp Dermatol 2006;31:807)
- Oral mucosa, skin deep rete ridges (Differentiation 2004;72:387)
- Stratified epithelium basal regions (cervix) (Am J Pathol 1993;142:403)
- Positive staining - disease:
- Paget's disease: extramammary (small, compressed keratinocytes) (Histopathology 2006;48:723)
- Sebaceomas (J Cutan Pathol 2006;33:634)
- Trichoepithelioma (63 - 100%) (Eur J Dermatol 1999;9:363, J Cutan Pathol 1999;26:113)
- Negative staining: cornea (central), sebaceous carcinomas and sebaceous neoplasms in Muir-Torre syndrome
- Reference: OMIM 148030
Cytokeratin 16 (CK16)
- Molecular weight of 48 kDa
- Paired with keratin 6
- Activated keratinocytes produce keratin 6, 16, 17, not normally present (Am J Pathol 1998;152:1133)
- Upregulated in benign keratinocyte hyperplasia, including psoriasis; prepsoriatic skin may be converted to a distinct adult tissue type resembling hard palate (J Investig Dermatol Symp Proc 2006;11:16)
- Also upregulated in stress incontinence in periurethral vaginal wall, conjunctival epithelium in Sjogren’s syndrome (Hum Reprod 2006;21:22, Exp Eye Res 2003;77:17)
- Downregulated in cervical squamous carcinoma (Virology 2005;331:269)
- Mutations are associated with:
- Pachyonychia congenita (Nat Genet 1995;9:273)
- Focal nonepidermolytic palmoplantar keratoderma (Hum Mol Genet 1995;4:1875)
- Uses by pathologists: no significant clinical use by pathologists
- Positive staining - normal:
- Esophagus
- Hair, nail and glands of epidermis
- Melanocytes (Am J Dermatopathol 2005;27:476)
- Positive staining - disease:
- Keratoderma of the palms (strong) (Acta Dermatovenerol Croat 2005;13:206)
- Skin damage (suprabasal keratinocytes)
- Tympanic membrane: annular region (Acta Otolaryngol 1993;113:345)
- Positive staining - malignant:
- Breast: invasive (10%) (Am J Pathol 1991;138:751)
- Squamous cell carcinoma in situ of skin: clear cell type (J Cutan Pathol 2007;34:226)
- Negative staining: normal breast
- Reference: OMIM 148067
Cytokeratin KL-1
- Broad spectrum keratin antibody for CK1 - 4, 10 - 11 or CK1, 2, 5 - 8, 11, 14, 16 - 18 (Jpn J Clin Oncol 1998;28:480)
- Not used as frequently as AE1 / AE3
- Uses by pathologists:
- Detect tumor cells in bone marrow (Jpn J Clin Oncol 1998;28:480)
- Detect micrometastases in lymph nodes (Mod Pathol 2002;15:641)
- Label tumor cells for flow cytometry from archival specimens (Am J Clin Pathol 1998;110:227)
- Positive staining - normal: most epithelium (J Invest Dermatol 1983;81:351)
- Positive staining - disease: most carcinomas; craniopharyngioma; liver epithelial neoplasms (Acta Neurochir (Wien) 2001;143:147, Am J Pathol 1987;127:530)
Microscopic (histologic) images
Images hosted on other servers:
CK3: suprabasal staining
of limbus epithelium
cultured using
airlifting technique
