Cytokeratins-AE1/AE3

Sources/Clones
Dako (AE1/AE3), Zymed (AE1, AE3).

Fixation/Preparation
This antibody is suitable for immunohistochemical staining of formalin-fixed, paraffin-embedded or frozen tissue sections. Trypsin or pepsin digestion/antigen retrieval is necessary before staining of formalin-fixed, paraffin-embedded tissue sections, although pepsin has been found to be superior to trypsin. The Zymed antibody is prediluted and ready to use. However, if DAB is used as a chromogen for immunodetection, then a further dilution of the primary antibody may be required.

Background
The antibody AE1/AE3 is a mixture of two monoclonal antibodies, raised against human epidermal keratins (Woodcock-Mitchell et al, 1982). AE1 recognizes most of the acidic (type 1) keratins with molecular weights 56.5, 50, 501, 48 and 40 kD.AE3 recognizes all known basic (type II) cytokeratins (Moll et al, 1982). This combination shows broad reactivity and is claimed to stain almost all epithelia and their neoplasms. It is also reputed not to crossreact with other members of the intermediate filaments.

Applications
The wide reactivity of AE1/AE3 expressed in simple epithelia and their tumors, including cytokeratins expressed in complex stratified squamous epithelia, permits identification of a wide range of epithelial-derived tumors. Hence, strong staining of AE1/AE3 has been demonstrated in adenocarcinomas (e.g. colorectal, gastric, breast, prostate), renal cell carcinoma, hepatocellular carcinoma, transitional cell carcinoma, small cell carcinoma, carcinoid tumors, epithelial component of pleomorphic adenoma and squamous cell carcinoma of the skin (including the spindle cell variant), cervix and bronchus. Thymomas, mesotheliomas (including the sarcomatoid component) and chordomas consistently stain with AE1/AE3. Non-epithelial tumors that demonstrate AE1/AE3 positivity include germ cell tumors (except seminomas), synovial sarcoma and epithelioid sarcoma. Crossreactivity in some leiomyosarcomas has been documented (Tseng et al, 1982; Spagnolo et al, 1983; Battifora, 1988; Goddard et al, 1991).
In a recent study of 290 cases of hepatocellular carcinoma, immunohistochemical evidence of biliary differentiation (reactivity with AE1/AE3 or cytokeratin 19) was found in 29.3% of cases. These hepatocellular carcinomas with biliary differentiation showed clinical features of greater aggressiveness with poorer cellular differentiation and higher expression of proliferation markers (Wu et al, 1996).

Comments
The pankeratin marking potential of antibody AE1/AE3 places it in an ideal position to screen for neoplasms of epithelial origin, especially poorly differentiated carcinomas of diverse origin, and to distinguish these from melanoma and lymphoma. Another useful role is the identification of micrometastases, e.g. breast secondaries in lymph nodes and bone marrow.

References
•Battifora H 1988. Diagnostic uses of antibodies to keratins: a review and immunohistochemical comparison of seven monoclonal and three polyclonal antibodies. In: Fenoglio-Preiser CM, Wolff M, Rilke F (eds)

•Progress in surgical pathology, vol VIII. Berlin: Springer-Verlag, pp 1-15.

•Goddard MJ, Wilson B, Grant JW 1991. Comparison of commercially available cytokeratin antibodies in normal and neoplastic adult epithelial and nonepithelial tissues. Journal of Clinical Pathology 44:660-663.

•Moll R, Franke WW, Schiller DL, Geiger B, Krepler R 1982. The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. Cell 31: 11-24.

•Spagnolo DV, Michie SA, Crabtree GS, Warnke RA, Ronse RV 1983. Monoclonal anti-keratin (AE1) reactivity in routinely processed tissue from 166 human neoplasms. American Journal of Clinical Pathology 84: 697-704.

•Tseng SCG, Jarvinen M, Nelson WG, Twang J-W, Woodcock-Mitchell J, Sun T-T 1982. Correlation of specific keratin with different types of epithelial differentiation: monoclonal antibody studies. Cell 30: 361-372.

•Woodcock-Mitchell J, Eichner R, Nelson WG, Sun T-T 1982. Immunolocalisation of keratin polypeptides in human epidermis using monoclonal antibodies. Journal of Cell Biology 95: 580-588.

•Wu PC, Fang JWS, Lau VKT et al 1996. Classification of hepatocellular carcinoma according to hepatocellular and biliary differentiation markers, clinical and biological implications. American Journal of Pathology 149: 1167-1175.

Bibliografía
Manual of diagnostic antibodies for immunohistology / Anthony S.-Y. Leong, Kumarasen Cooper, F. Joel W.-M. Leong.

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