Logo of amjpatholAmerican Journal of Pathology For AuthorsAmerican Journal of Pathology SubscribeAmerican Journal of Pathology SearchAmerican Journal of Pathology Current IssueAmerican Journal of Pathology About the JournalAmerican Journal of Pathology
Am J Pathol. 1992 Feb; 140(2): 427–447.
PMCID: PMC1886432

Cytokeratin 20 in human carcinomas. A new histodiagnostic marker detected by monoclonal antibodies.


The authors have recently identified a new cytokeratin (CK) polypeptide, CK 20, whose expression is almost entirely confined to the gastric and intestinal epithelium, urothelium, and Merkel cells. Seven monoclonal antibodies (MAbs) specific for CK 20 were raised and characterized by applying immunoblotting and immunocytochemical screening. All of them reacted on frozen tissue sections. A further MAb, IT-Ks20.8, recognized CK 20 in sections of formalin-fixed, paraffin-embedded tissue samples. A total of 711 cases of primary and metastatic cancer, mostly carcinomas, were analyzed immunohistochemically for CK-20 expression, using CK-20 specific guinea-pig antibodies and MAbs. The expression spectrum of CK 20 in carcinomas resembled that seen in the corresponding normal epithelia of origin. CK-20 positivity was seen in the vast majority of adenocarcinomas of the colon (89/93 cases), mucinous ovarian tumors, transitional-cell and Merkel-cell carcinomas and frequently also in adenocarcinomas of the stomach, bile system, and pancreas. Most squamous cell carcinomas in general and most adenocarcinomas from other sites (breast, lung, endometrium), nonmucinous tumors of the ovary, and small-cell lung carcinomas were essentially or completely negative. The authors propose to use CK 20 as a diagnostic marker valuable in distinguishing different types of carcinomas, notably when presenting as metastases.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (6.5M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Osborn M, Weber K. Tumor diagnosis by intermediate filament typing: a novel tool for surgical pathology. Lab Invest. 1983 Apr;48(4):372–394. [PubMed]
  • Nagle RB. Intermediate filaments: a review of the basic biology. Am J Surg Pathol. 1988;12 (Suppl 1):4–16. [PubMed]
  • Nagle RB. Intermediate filaments. Efficacy in surgical pathologic diagnosis. Am J Clin Pathol. 1989 Apr;91(4 Suppl 1):S14–S18. [PubMed]
  • Fuchs E, Green H. Changes in keratin gene expression during terminal differentiation of the keratinocyte. Cell. 1980 Apr;19(4):1033–1042. [PubMed]
  • Franke WW, Schiller DL, Moll R, Winter S, Schmid E, Engelbrecht I, Denk H, Krepler R, Platzer B. Diversity of cytokeratins. Differentiation specific expression of cytokeratin polypeptides in epithelial cells and tissues. J Mol Biol. 1981 Dec 25;153(4):933–959. [PubMed]
  • Moll R, Franke WW, Schiller DL, Geiger B, Krepler R. The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. Cell. 1982 Nov;31(1):11–24. [PubMed]
  • Tseng SC, Jarvinen MJ, Nelson WG, Huang JW, Woodcock-Mitchell J, Sun TT. Correlation of specific keratins with different types of epithelial differentiation: monoclonal antibody studies. Cell. 1982 Sep;30(2):361–372. [PubMed]
  • Wu YJ, Parker LM, Binder NE, Beckett MA, Sinard JH, Griffiths CT, Rheinwald JG. The mesothelial keratins: a new family of cytoskeletal proteins identified in cultured mesothelial cells and nonkeratinizing epithelia. Cell. 1982 Dec;31(3 Pt 2):693–703. [PubMed]
  • Moll R, Krepler R, Franke WW. Complex cytokeratin polypeptide patterns observed in certain human carcinomas. Differentiation. 1983;23(3):256–269. [PubMed]
  • Quinlan RA, Schiller DL, Hatzfeld M, Achtstätter T, Moll R, Jorcano JL, Magin TM, Franke WW. Patterns of expression and organization of cytokeratin intermediate filaments. Ann N Y Acad Sci. 1985;455:282–306. [PubMed]
  • Fuchs E, Tyner AL, Giudice GJ, Marchuk D, RayChaudhury A, Rosenberg M. The human keratin genes and their differential expression. Curr Top Dev Biol. 1987;22:5–34. [PubMed]
  • Cooper D, Schermer A, Sun TT. Classification of human epithelia and their neoplasms using monoclonal antibodies to keratins: strategies, applications, and limitations. Lab Invest. 1985 Mar;52(3):243–256. [PubMed]
  • Moll R. Epithelial tumor markers: cytokeratins and tissue polypeptide antigen (TPA). Curr Top Pathol. 1987;77:71–101. [PubMed]
  • Gown AM, Vogel AM. Monoclonal antibodies to human intermediate filament proteins. III. Analysis of tumors. Am J Clin Pathol. 1985 Oct;84(4):413–424. [PubMed]
  • Ramaekers F, Huysmans A, Moesker O, Kant A, Jap P, Herman C, Vooijs P. Monoclonal antibody to keratin filaments, specific for glandular epithelia and their tumors. Use in surgical pathology. Lab Invest. 1983 Sep;49(3):353–361. [PubMed]
  • Debus E, Moll R, Franke WW, Weber K, Osborn M. Immunohistochemical distinction of human carcinomas by cytokeratin typing with monoclonal antibodies. Am J Pathol. 1984 Jan;114(1):121–130. [PMC free article] [PubMed]
  • Bártek J, Bártková J, Taylor-Papadimitriou J, Rejthar A, Kovarík J, Lukás Z, Vojtesek B. Differential expression of keratin 19 in normal human epithelial tissues revealed by monospecific monoclonal antibodies. Histochem J. 1986 Oct;18(10):565–575. [PubMed]
  • Osborn M, van Lessen G, Weber K, Klöppel G, Altmannsberger M. Differential diagnosis of gastrointestinal carcinomas by using monoclonal antibodies specific for individual keratin polypeptides. Lab Invest. 1986 Oct;55(4):497–504. [PubMed]
  • Shah KD, Tabibzadeh SS, Gerber MA. Comparison of cytokeratin expression in primary and metastatic carcinomas. Diagnostic application in surgical pathology. Am J Clin Pathol. 1987 Jun;87(6):708–715. [PubMed]
  • Osborn M, Mazzoleni G, Santini D, Marrano D, Martinelli G, Weber K. Villin, intestinal brush border hydrolases and keratin polypeptides in intestinal metaplasia and gastric cancer; an immunohistologic study emphasizing the different degrees of intestinal and gastric differentiation in signet ring cell carcinomas. Virchows Arch A Pathol Anat Histopathol. 1988;413(4):303–312. [PubMed]
  • Ramaekers F, van Niekerk C, Poels L, Schaafsma E, Huijsmans A, Robben H, Schaart G, Vooijs P. Use of monoclonal antibodies to keratin 7 in the differential diagnosis of adenocarcinomas. Am J Pathol. 1990 Mar;136(3):641–655. [PMC free article] [PubMed]
  • Denk H, Krepler R, Lackinger E, Artlieb U, Franke WW. Biochemical and immunocytochemical analysis of the intermediate filament cytoskeleton in human hepatocellular carcinomas and in hepatic neoplastic nodules of mice. Lab Invest. 1982 Jun;46(6):584–596. [PubMed]
  • Fischer HP, Altmannsberger M, Weber K, Osborn M. Keratin polypeptides in malignant epithelial liver tumors. Differential diagnostic and histogenetic aspects. Am J Pathol. 1987 Jun;127(3):530–537. [PMC free article] [PubMed]
  • Van Eyken P, Sciot R, Paterson A, Callea F, Kew MC, Desmet VJ. Cytokeratin expression in hepatocellular carcinoma: an immunohistochemical study. Hum Pathol. 1988 May;19(5):562–568. [PubMed]
  • Blobel GA, Moll R, Franke WW, Kayser KW, Gould VE. The intermediate filament cytoskeleton of malignant mesotheliomas and its diagnostic significance. Am J Pathol. 1985 Nov;121(2):235–247. [PMC free article] [PubMed]
  • Moll R, Dhouailly D, Sun TT. Expression of keratin 5 as a distinctive feature of epithelial and biphasic mesotheliomas. An immunohistochemical study using monoclonal antibody AE14. Virchows Arch B Cell Pathol Incl Mol Pathol. 1989;58(2):129–145. [PubMed]
  • Altman E, Cadman E. An analysis of 1539 patients with cancer of unknown primary site. Cancer. 1986 Jan 1;57(1):120–124. [PubMed]
  • Ellis IO, Hitchcock A. Tumour marker immunoreactivity in adenocarcinoma. J Clin Pathol. 1988 Oct;41(10):1064–1067. [PMC free article] [PubMed]
  • Kabawat SE, Bast RC, Welch WR, Knapp RC, Colvin RB. Immunopathologic characterization of a monoclonal antibody that recognizes common surface antigens of human ovarian tumors of serous, endometrioid, and clear cell types. Am J Clin Pathol. 1983 Jan;79(1):98–104. [PubMed]
  • Gröne HJ, Weber K, Helmchen U, Osborn M. Villin--a marker of brush border differentiation and cellular origin in human renal cell carcinoma. Am J Pathol. 1986 Aug;124(2):294–302. [PMC free article] [PubMed]
  • Moll R, Robine S, Dudouet B, Louvard D. Villin: a cytoskeletal protein and a differentiation marker expressed in some human adenocarcinomas. Virchows Arch B Cell Pathol Incl Mol Pathol. 1987;54(3):155–169. [PubMed]
  • Vojtesek B, Stasková Z, Nenutil R, Bártková J, Kovarík J, Rejthar A, Bártek J. A panel of monoclonal antibodies to keratin no. 7: characterization and value in tumor diagnosis. Neoplasma. 1990;37(3):333–342. [PubMed]
  • Moll R, Pitz S, Levy R, Weikel W, Franke WW, Czernobilsky B. Complexity of expression of intermediate filament proteins, including glial filament protein, in endometrial and ovarian adenocarcinomas. Hum Pathol. 1991 Oct;22(10):989–1001. [PubMed]
  • Azumi N, Battifora H. The distribution of vimentin and keratin in epithelial and nonepithelial neoplasms. A comprehensive immunohistochemical study on formalin- and alcohol-fixed tumors. Am J Clin Pathol. 1987 Sep;88(3):286–296. [PubMed]
  • Moll R, Schiller DL, Franke WW. Identification of protein IT of the intestinal cytoskeleton as a novel type I cytokeratin with unusual properties and expression patterns. J Cell Biol. 1990 Aug;111(2):567–580. [PMC free article] [PubMed]
  • Pruss RM, Mirsky R, Raff MC, Thorpe R, Dowding AJ, Anderton BH. All classes of intermediate filaments share a common antigenic determinant defined by a monoclonal antibody. Cell. 1981 Dec;27(3 Pt 2):419–428. [PubMed]
  • Achtstaetter T, Hatzfeld M, Quinlan RA, Parmelee DC, Franke WW. Separation of cytokeratin polypeptides by gel electrophoretic and chromatographic techniques and their identification by immunoblotting. Methods Enzymol. 1986;134:355–371. [PubMed]
  • Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [PubMed]
  • Kyhse-Andersen J. Electroblotting of multiple gels: a simple apparatus without buffer tank for rapid transfer of proteins from polyacrylamide to nitrocellulose. J Biochem Biophys Methods. 1984 Dec;10(3-4):203–209. [PubMed]
  • Köhler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975 Aug 7;256(5517):495–497. [PubMed]
  • Moll R, Achtstätter T, Becht E, Balcarova-Ständer J, Ittensohn M, Franke WW. Cytokeratins in normal and malignant transitional epithelium. Maintenance of expression of urothelial differentiation features in transitional cell carcinomas and bladder carcinoma cell culture lines. Am J Pathol. 1988 Jul;132(1):123–144. [PMC free article] [PubMed]
  • Achtstätter T, Fouquet B, Rungger-Brändle E, Franke WW. Cytokeratin filaments and desmosomes in the epithelioid cells of the perineurial and arachnoidal sheaths of some vertebrate species. Differentiation. 1989 May;40(2):129–149. [PubMed]
  • Wiedenmann B, Franke WW. Identification and localization of synaptophysin, an integral membrane glycoprotein of Mr 38,000 characteristic of presynaptic vesicles. Cell. 1985 Jul;41(3):1017–1028. [PubMed]
  • Franke WW, Moll R. Cytoskeletal components of lymphoid organs. I. Synthesis of cytokeratins 8 and 18 and desmin in subpopulations of extrafollicular reticulum cells of human lymph nodes, tonsils, and spleen. Differentiation. 1987;36(2):145–163. [PubMed]
  • Hsu SM, Raine L, Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577–580. [PubMed]
  • Moll R, Levy R, Czernobilsky B, Hohlweg-Majert P, Dallenbach-Hellweg G, Franke WW. Cytokeratins of normal epithelia and some neoplasms of the female genital tract. Lab Invest. 1983 Nov;49(5):599–610. [PubMed]
  • Blobel GA, Moll R, Franke WW, Vogt-Moykopf I. Cytokeratins in normal lung and lung carcinomas. I. Adenocarcinomas, squamous cell carcinomas and cultured cell lines. Virchows Arch B Cell Pathol Incl Mol Pathol. 1984;45(4):407–429. [PubMed]
  • Moll R, Franke WW. Cytoskeletal differences between human neuroendocrine tumors: a cytoskeletal protein of molecular weight 46,000 distinguishes cutaneous from pulmonary neuroendocrine neoplasms. Differentiation. 1985;30(2):165–175. [PubMed]
  • Huszar M, Gigi-Leitner O, Moll R, Franke WW, Geiger B. Monoclonal antibodies to various acidic (type I) cytokeratins of stratified epithelia. Selective markers for stratification and squamous cell carcinomas. Differentiation. 1986;31(2):141–153. [PubMed]
  • van Muijen GN, Ruiter DJ, Franke WW, Achtstätter T, Haasnoot WH, Ponec M, Warnaar SO. Cell type heterogeneity of cytokeratin expression in complex epithelia and carcinomas as demonstrated by monoclonal antibodies specific for cytokeratins nos. 4 and 13. Exp Cell Res. 1986 Jan;162(1):97–113. [PubMed]
  • Dockhorn-Dworniczak B, Franke WW, Schröder S, Czernobilsky B, Gould VE, Böcker W. Patterns of expression of cytoskeletal proteins in human thyroid gland and thyroid carcinomas. Differentiation. 1987;35(1):53–71. [PubMed]
  • Morgan PR, Shirlaw PJ, Johnson NW, Leigh IM, Lane EB. Potential applications of anti-keratin antibodies in oral diagnosis. J Oral Pathol. 1987 Apr;16(4):212–222. [PubMed]
  • Pitz S, Moll R, Störkel S, Thoenes W. Expression of intermediate filament proteins in subtypes of renal cell carcinomas and in renal oncocytomas. Distinction of two classes of renal cell tumors. Lab Invest. 1987 Jun;56(6):642–653. [PubMed]
  • Broers JL, Ramaekers FC, Rot MK, Oostendorp T, Huysmans A, van Muijen GN, Wagenaar SS, Vooijs GP. Cytokeratins in different types of human lung cancer as monitored by chain-specific monoclonal antibodies. Cancer Res. 1988 Jun 1;48(11):3221–3229. [PubMed]
  • Morgan Peter P. Dr. Morgan responds. CMAJ. 1993 Aug 01;149(3):b264–264. [PMC free article]
  • Moll R, Osborn M, Hartschuh W, Moll I, Mahrle G, Weber K. Variability of expression and arrangement of cytokeratin and neurofilaments in cutaneous neuroendocrine carcinomas (Merkel cell tumors): immunocytochemical and biochemical analysis of twelve cases. Ultrastruct Pathol. 1986;10(6):473–495. [PubMed]
  • Nicolson GL. Tumor cell instability, diversification, and progression to the metastatic phenotype: from oncogene to oncofetal expression. Cancer Res. 1987 Mar 15;47(6):1473–1487. [PubMed]
  • Knapp AC, Franke WW. Spontaneous losses of control of cytokeratin gene expression in transformed, non-epithelial human cells occurring at different levels of regulation. Cell. 1989 Oct 6;59(1):67–79. [PubMed]
  • Yeger H, Baumal R, Kahn HJ, Duwe G, Phillips MJ. The use of cytoskeletal characteristics of tumor cells for the diagnosis of colon and breast adenocarcinomas. Am J Clin Pathol. 1986 Dec;86(6):697–705. [PubMed]
  • Gould VE, Moll R, Moll I, Lee I, Franke WW. Neuroendocrine (Merkel) cells of the skin: hyperplasias, dysplasias, and neoplasms. Lab Invest. 1985 Apr;52(4):334–353. [PubMed]
  • Hoefler H, Kerl H, Rauch HJ, Denk H. New immunocytochemical observations with diagnostic significance in cutaneous neuroendocrine carcinoma. Am J Dermatopathol. 1984 Dec;6(6):525–530. [PubMed]
  • Lehto VP, Stenman S, Miettinen M, Dahl D, Virtanen I. Expression of a neural type of intermediate filament as a distinguishing feature between oat cell carcinoma and other lung cancers. Am J Pathol. 1983 Feb;110(2):113–118. [PMC free article] [PubMed]
  • Achtstätter T, Moll R, Moore B, Franke WW. Cytokeratin polypeptide patterns of different epithelia of the human male urogenital tract: immunofluorescence and gel electrophoretic studies. J Histochem Cytochem. 1985 May;33(5):415–426. [PubMed]
  • Schaafsma HE, Ramaekers FC, van Muijen GN, Lane EB, Leigh IM, Robben H, Huijsmans A, Ooms EC, Ruiter DJ. Distribution of cytokeratin polypeptides in human transitional cell carcinomas, with special emphasis on changing expression patterns during tumor progression. Am J Pathol. 1990 Feb;136(2):329–343. [PMC free article] [PubMed]
  • Reedy EA, Heatfield BM, Trump BF, Resau JH. Correlation of cytokeratin patterns with histopathology during neoplastic progression in the rat urinary bladder. Pathobiology. 1990;58(1):15–27. [PubMed]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Cited in Books
    Cited in Books
    PubMed Central articles cited in books
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...