Home Chapter Home Jobs Conferences Fellowships Books
Advertisement
Stains
Cytokeratin AE1/AE3
Authors: Kara Hamilton, M.S., Nat Pernick, M.D., PathologyOutlines.com, Inc.
Revised: 15 April 2010, last major update - June 2009
Copyright: (c) 2002-2010, PathologyOutlines.com, Inc.
Definition
=========================================================================
● Keratin cocktail that detects CK1-8, 10, 14-16 and 19
● Does not detect CK17 or CK18; for this reason, some pan-keratin cocktails also contain CAM5.2 (detects CK18)
Terminology
=========================================================================
● Often referred to in literature as “keratin” or “pankeratin”
Uses
=========================================================================
(1) 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)
(2) identify metastatic carcinoma in lymph nodes (Gynecol Oncol. 2007 Jun;105(3):683) or bone marrow (Int J Cancer 2007;120:1603) 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 (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 Cancer 2006;16:1188), endobronchial carcinoid (Ann Thorac Surg 2005;80:428), GE junction (Eur J Surg Oncol 2005;31:270), lung-nonsmall cell (with p53-Ann Surg 2002;235:133 / Eur J Cardiothorac Surg 2007;31:1120), 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 nonsmall 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)
(3) 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 (AJSP 2007;31:390)
(4) assess depth of invasion (Int J Gynecol Cancer 2004;14:665)
(5) establish presence of noninvasive epithelial downgrowth after penetrating keratoplasty (Cornea 2006;25:727)
(6) part of flow cytometry strategy to enrich epithelial cells in sputum (Cytometry A 2004;60:1)
Interpretation
=========================================================================
● May cross react with GFAP, leading to aberrant staining of glial tumors (ependymoma, glioblastoma, schwannoma, Mod Path 2006;19:115)
● Note: staining pattern of cocktail may be different than staining pattern of AE1 and AE3 separately due to different pretreatment
Positive stains - normal
=========================================================================
● Most epithelium
● Adenohypophysis follicular cells (Pathol Int 2005;55:244), trophoblast (AJCP 1991;95:137)
Positive stains - disease
=========================================================================
● Most carcinomas
● Adenomatoid tumor (Histopathology 2000;36:109, AJSP 2003;27:969)
● Adenomatoid odontogenic tumor (Oral Oncol 2005;41:835)
● Aggressive angiomyxoma (27%, Virchows Arch 2005;446:157)
● Angiosarcoma-GI tract (AJSP 2004;28:298) and epithelioid (Ann Diagn Pathol 2005;9:33)
● Chordoma (Clin Neuropathol 2004;23:277)
● Choroid plexus tumors (Arq Neuropsiquiatr 2004;62:600)
● Cylindroma (AJSP 2001;25:823)
● Desmoplastic round cell tumor (Cytojournal 2005;2:6)
● Ependymoma (Appl Immunohistochem Mol Morphol 2000;8:25)
● Epithelioid hemangioendothelioma (focal, Int J Surg Pathol 2000;8:75)
● Epithelioid sarcoma (J Cutan Pathol 2004;31:67)
● Female adnexal tumor of probable wolffian origin (Hum Path 1999;30:856)
● GI tract-reactive nodular fibrous pseudotumor (Int J Surg Pathol 2004;12:365)
● Glioblastoma multiforme and gliomas (AJSP 1989;13:141)
● Hepatoblastoma (Pediatr Dev Pathol 2006;9:196)
● Meningioma-malignant (75%, Mod Path 2004;17:1129)
● Mesothelioma (Pathol Int 2007;57:190, AJSP 2007;31:711)
● Myoepithelial tumors (AJSP 2003;27:1183)
● Paraganglioma of cauda equina (Hum Path 2005;36:444)
● Pituitary carcinoma (Acta Cytol 2006;50:225)
● Prostate carcinoma neuroendocrine cells (Prostate 2006;66:1399)
● Schwannoma (69% of retroperitoneum tumors, Mod Path 2006;19:115)
● Sertoli cell tumor (Hum Path 1992;23:787)
● Synovial sarcoma (usually, AJSP 2002;26:1434)
● Testicular/epididymal papillary cystadenoma (AJSP 2005;29:520)
● Thymoma (Virchows Arch A Pathol Anat Histopathol 1992;420:185)
● Trophoblastic tumors (AJSP 2004;28:405)
● Yolk sac tumor (Diagn Cytopathol 2006;34:421)
Negative stains
=========================================================================
● Adrenocortical carcinoma (often)
● Dysgerminoma (8% positive, Hum Path 2006;37:1015)
● Endometrial stromal sarcoma (24% positive, Mod Path 2005;18:40)
● Hepatocellular carcinoma (15% positive, Mod Path 1989;2:8)
● Ovarian sex cord stromal tumors (27% positive, Zhonghua Bing Li Xue Za Zhi 2004;33:217, but Sertoli cell tumors are positive)
● Paraganglioma (Ann Diagn Pathol 2004;8:237)
● Sclerosing epithelioid fibrosarcoma (usually, Zhonghua Bing Li Xue Za Zhi 2004;33:337)
● Seminoma (usually negative, AJSP 2005;29:500, but 20% of retroperitoneal tumors are positive, AJSP 2006;30:766)
● Wilm’s tumor-epithelial component (Sao Paulo Med J 2004;122 (4))
Micro images
=========================================================================
adenomatoid tumor #1-adrenal gland (fig b); #2-testis
adrenocortical carcinoma-oncocytic
angiosarcoma #1 (fig 2); #2 (fig 1C-AE1-AE3 and CAM5.2)
bladder-lymphoepithelioma like carcinoma
breast-angiomyoepithelioma-malignant-fig C shows staining of epithelial component
breast carcinoma-lobular-metastasis to endometrial polyp #1; #2
breast carcinoma-sentinel node #1 is AE1-AE3+; #2
colon-isolated tumor cells #1; #2; #3; #4
kidney-atypical angiomyolipoma (left) is negative, normal kidney (right) is positive
lung cancer (nonsmall cell) associated lymph node
nasal cavity-myoepithelial carcinoma
nasal cavity-small cell carcinoma (fig 1D)
neuroendocrine carcinoma-duodenum
salivary gland #1-acinic cell carcinoma (fig 4); #2-epithelial-myoepithelial carcinoma; #3-undifferentiated sarcoma-normal ducts but not tumor are AE1-AE3+
pleura-poorly differentiated carcinoma
sarcomatoid carcinoma-small bowel (fig 3a)
skin-basal cell carcinoma metastasis to bone (fig 4)
skin-squamous cell carcinoma in situ
skin-squamous cell carcinoma-acantholytic type
squamous cell carcinoma-site unknown
stomach-signet ring cell carcinoma
thyroid anaplastic carcinoma #1; #2
Virtual slides
=========================================================================
diffuse large B cell lymphoma (negative); positive control (? thymus)
Additional references
=========================================================================
Sources for AE1/AE3 (advertisements): Covance
End of Stains > Cytokeratin AE1/AE3
This information is intended for physicians and related personnel, who understand that medical information is often imperfect, and must also be interpreted in the context of a patient's clinical data using reasonable medical judgment. This website should not be used as a substitute for the advice of a licensed physician.
All information on this website is protected by Copyright, (c) 2001-2009, PathologyOutlines.com, Inc. Information from third parties may also be protected by copyright. Please contact us at copyrightPathOut@gmail.com with any questions.