Cytokeratin AE1 / AE3

Stains & molecular markers
Cytokeratin AE1 / AE3

Author: Nat Pernick, M.D.

Topic Completed: 1 July 2013

Minor changes: 8 October 2020

Copyright: 2003-2021, PathologyOutlines.com, Inc.

PubMed Search: Cytokeratin AE1 / AE3

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Table of Contents

Cite this page: Pernick N. Cytokeratin AE1 / AE3. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsae1ae3.html. Accessed January 17th, 2021.

Definition / general

Keratin cocktail that detects CK1 - 8, 10, 14 - 16 and 19, but does not detect CK17 or CK18
Often referred to in literature as "keratin" or "pankeratin", although this may also refer to Cytokeratin MNF116
May cross react with GFAP, leading to aberrant staining of glial tumors (ependymoma, glioblastoma, schwannoma, Mod Pathol 2006;19:115)
Note: staining pattern of cocktail may be different than staining pattern of AE1 and AE3 separately, due to different pretreatment

Uses by pathologists

Confirm or rule out epithelial nature of tissue, tumors or components of tumors (example: breast ductal lavage foam cells are not epithelial, Diagn Cytopathol 2002;27:261)
Identify metastatic carcinoma in lymph nodes (Gynecol Oncol 2007;105:683, J Clin Pathol 2006;59:518), bone marrow (Int J Cancer 2007;120:1603) or at frozen section (Acta Histochem Cytochem 2011;44:133) by immunohistochemistry or (uncommonly) flow cytometry (J Thorac Cardiovasc Surg 2005;130:753)
- Note 1: nodal epithelial cells may represent artifact of recent biopsy, not metastatic disease (Ann Surg Oncol 2002;9:999)
- Note 2: hyalinized cytokeratin particles, without tumor cell nuclei, may cause misinterpretation (J Surg Res 2002;107:75)
- Note 3: may rarely stain nodal reticulum cells (Appl Immunohistochem Mol Morphol 2001;9:297)
- Note 4: presence of isolated nodal tumor cells / micrometastases in carcinoma has no apparent prognostic significance in carcinomas of breast (Appl Immunohistochem Mol Morphol 2006;14:426), colorectum (Clin Transl Oncol 2006;8:676), rectum (Int J Colorectal Dis 2007;22:911) and breast DCIS (Ann Surg Oncol 2005;12:254), but is a poor prognostic factor in carcinomas of cervix (Int J Gynecol Cance 2006;16:1188), endobronchial carcinoid (Ann Thorac Surg 2005;80:428), GE junction (Eur J Surg Oncol 2005;31:270), lung - nonsmall cell (Ann Surg 2002;235:133, Eur J Cardiothorac Surg 2007;31:1120) and stomach (Cancer 2002;94:2867)
- Note 5: the presence of isolated tumor cells / micrometastases in bone marrow is a poor prognostic factor in breast carcinoma (Clin Cancer Res 2004;10:5342), but not in non small cell lung carcinoma (Cancer 2004;100:794)
- Note 6: the presence of lymphovascular invasion detected only by immunohistochemistry has no prognostic value in endometrioid endometrial carcinoma (Gynecol Oncol 2004;92:653)
Identify residual tumor post treatment (example: prostate carcinoma post hormonal treatment - Hinyokika Kiyo 2006;52:781)
- Note: when trying to identify residual tumor cells, must pay attention to nature of cells, since AE1 / AE3 may stain myofibroblasts and smooth muscle cells (Am J Surg Pathol 2007;31:390)
Assess depth of invasion (Int J Gynecol Cancer 2004;14:665)
Establish presence of noninvasive epithelial downgrowth after penetrating keratoplasty (Cornea 2006;25:727)
Part of flow cytometry strategy to enrich epithelial cells in sputum (Cytometry A 2004;60:1)

Microscopic (histologic) images

Contributed by Andrey Bychkov, M.D., Ph.D.

MALT lymphoma

Strongly positive cancer
cells versus weakly positive
thyroid follicles

Cytology images

Cases #54 and 32

Salivary gland:
epithelial-
myoepithelial
carcinoma

Thyroid anaplastic carcinoma

Kidney: atypical
angiomyolipoma

Images hosted on other servers:

Various stains

Breast lobular carcinoma: metastasis to lymph node - H&E and AE1 / AE3

Duodenum: neuroendocrine carcinoma

Liver: adenomatoid tumor

Lung cancer
(non small cell)
associated
lymph node

Lung cancer (non small cell) associated lymph node: frozen section

Oral cavity:
squamous cell
carcinoma -
acantholytic type

Pleura: sarcomatoid mesothelioma

Soft tissue: benign mixed tumor

Soft tissue: myoepithelioma

Soft tissue: myxoid chondrosarcoma

Spinal cord:
myxopapillary
ependymoma of
filum terminale

Testis: yolk sac tumor

Positive staining - normal

Most epithelium
Adenohypophysis follicular cells (Pathol Int 2005;55:244), trophoblast (Am J Clin Pathol 1991;95:137)

Positive staining - disease

Most carcinomas
Adenomatoid tumor (Histopathology 2000;36:109, Am J Surg Pathol 2003;27:969)
Adenomatoid odontogenic tumor (Oral Oncol 2005;41:835)
Aggressive angiomyxoma (27%, Virchows Arch 2005;446:157)
Angiosarcoma - GI tract (Am J Surg Pathol 2004;28:298) and epithelioid (Ann Diagn Pathol 2005;9:33)
Chondroblastoma and chondrosarcoma - clear cell (60%, Hum Pathol 2013;44:237)
Chordoma (Clin Neuropathol 2004;23:277)
Choroid plexus tumors (Arq Neuropsiquiatr 2004;62:600)
Cylindroma (Am J Surg Pathol 2001;25:823)
Desmoplastic small round cell tumor (Cytojournal 2005;2:6)
Ependymoma (Appl Immunohistochem Mol Morphol 2000;8:25)
Epithelioid sarcoma (J Cutan Pathol 2004;31:67, Am J Surg Pathol 2011;35:891)
Female adnexal tumor of probable wolffian origin (Hum Pathol 1999;30:856)
GI tract - reactive nodular fibrous pseudotumor (Int J Surg Pathol 2004;12:365)
Glioblastoma multiforme and gliomas (Am J Surg Pathol 1989;13:141)
Hemangioendothelioma - epithelioid (focal, Int J Surg Pathol 2000;8:75) and pseudomyogenic (100%, Am J Surg Pathol 2011;35:190)
Hepatoblastoma (Pediatr Dev Pathol 2006;9:196)
Meningioma - malignant (75%, Mod Pathol 2004;17:1129)
Mesothelioma (Pathol Int 2007;57:190, Am J Surg Pathol 2007;31:711)
Myoepithelial tumors (Am J Surg Pathol 2003;27:1183)
Paraganglioma of cauda equina (Hum Pathol 2005;36:444)
Pituitary carcinoma (Acta Cytol 2006;50:225)
Proliferative fasciitis (46% positive, Am J Surg Pathol 2012;36:1404)
Prostate carcinoma neuroendocrine cells (Prostate 2006;66:1399)
Schwannoma (69% of retroperitoneum tumors, Mod Pathol 2006;19:115)
Sertoli cell tumor (Hum Pathol 1992;23:787)
Synovial sarcoma (usually, Am J Surg Pathol 2002;26:1434)
Testicular / epididymal papillary cystadenoma (Am J Surg Pathol 2005;29:520)
Thymoma (Virchows Arch A Pathol Anat Histopathol 1992;420:185)
Trophoblastic tumors (Am J Surg Pathol 2004;28:405)
Yolk sac tumor (Diagn Cytopathol 2006;34:421, Am J Surg Pathol 2012;36:360)

Negative stains

Adrenocortical carcinoma (often)
Digital fibromyxoma (Am J Surg Pathol 2012;36:789)
Dysgerminoma (8% positive, Hum Pathol 2006;37:1015)
Endometrial stromal sarcoma (24% positive, Mod Pathol 2005;18:40)
Hepatocellular carcinoma (15% positive, Mod Pathol 1989;2:8)
Lymphangioma (Hum Pathol 2011;42:1013)
Malignant fibrous histiocytoma (15% positive, Am J Surg Pathol 2012;36:1404)
Nodular fasciitis (9% positive, Am J Surg Pathol 2012;36:1404)
Ovarian sex cord stromal tumors (overall 27% positive, Zhonghua Bing Li Xue Za Zhi 2004;33:217; Sertoli cell tumors are generally positive)
Paraganglioma - lung (Ann Diagn Pathol 2004;8:237)
Sclerosing epithelioid fibrosarcoma (usually, Zhonghua Bing Li Xue Za Zhi 2004;33:337)
Seminoma (usually negative, Am J Surg Pathol 2005;29:500, but 20% of retroperitoneal tumors are positive, Am J Surg Pathol 2006;30:766)
Solitary fibrous tumor (11% positive, Am J Surg Pathol 2012;36:1404)
Wilm tumor - epithelial component (Sao Paulo Med J 2004;122:181)