Review
Intermediate filaments in oral neoplasia. I. Oral cancer and epithelial dysplasia

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Abstract

The major value of intermediate filaments (IFs) in biological and applied research lies in their high order of cell and tissue specificity. This is particularly well illustrated in keratin (K) expression in various oral epithelia. Although the original class of IF is usually conserved in tissues after neoplastic transformation, epithelia show a tendency to shift their pattern of keratin expression in a manner which, while not predictable with precision, may sometimes be of diagnostic or prognostic significance. This review compares the keratins in normal oral epithelia, which show a mainly site-dependent expression, with those in squamous cell carcinoma. Key changes in the latter are the presence of simple epithelial keratins, K8 and K18 (occasional K7), reduced expression of differentiation-linked keratins (K1, K10, K4 and K13) and a tendency for down-regulation of primary keratins, K5 and K14. Moderate and severe dysplasias also tend to exhibit K8 and K18 with concomitant disordered expression of differentiation-linked keratins. There are reports of similar changes after neoplastic transformation in other mucosal sites and skin. Before this information can be applied diagnostically in immunocytochemical studies, the anti-keratin antibodies must be fully characterised and their interaction with the relevant tissue, both frozen and conventionally processed, should be evaluated.

References (88)

  • CC Chipev et al.

    A leucine to proline mutation in the H1 subdomain of keratin 1 causes epidermolytic hyperkeratosis

    Cell

    (1992)
  • J Cheng et al.

    The genetic basis of epidermolytic hyperkeratosis: a disorder of differentiation-specific epidermal keratin genes

    Cell

    (1992)
  • KJ Green

    Structure of the human desmoplakins

    J Biol Chem

    (1990)
  • H Clausen et al.

    Differentiation-dependent expression of keratins in human oral epithelia

    J Invest Dermatol

    (1986)
  • JN Mansbridge et al.

    Changes in keratinocyte maturation during wound healing

    J Invest Dermatol

    (1987)
  • A Shabana et al.

    A comparative biochemical and immunological analysis of cytokeratin patterns in the oral epithelium of the miniature pig and man

    Arch Oral Biol

    (1989)
  • K Lindberg et al.

    Three distinct keratinocyte subtypes identified in human oral epithelium by their patterns of keratin expression in culture and in xenografts

    Differentiation

    (1990)
  • R Moll et al.

    An unusual type of cytokeratin filament in cells of a human cloacogenic carcinoma derived from the anorectal transition zone

    Differentiation

    (1982)
  • J Schulz et al.

    Cytokeratin pattern of clinically intact and pathologically changed oral mucosa

    Int J Oral Maxillofac Surg

    (1992)
  • AC Markey et al.

    Expression of simple epithelial keratins 8 and 18 in epidermal neoplasia

    J Invest Dermatol

    (1991)
  • PM Steinert et al.

    Intermediate filaments

    J Cell Biol

    (1984)
  • PM Steinert et al.

    Intermediate filaments: conformity and diversity of expression and structure

    Ann Rev Cell Biol

    (1985)
  • DR Roop et al.

    The structure and evolution of intermediate filament genes

  • PM Steinert et al.

    Molecular and cellular biology of intermediate filaments

    Ann Rev Biochem

    (1988)
  • E Lazarides

    Intermediate filaments as mechanical integrators of cellular space

    Nature

    (1980)
  • J Breckler et al.

    Isolation of a new high molecular weight protein associated with desmin and vimentin filaments from avian embryonic skeletal muscle

    J Cell Biol

    (1982)
  • R Moll et al.

    Identification of protein IT of the intestinal cytoskeleton as a novel type I cytokeratin with unusual properties and expression patterns

    J Cell Biol

    (1990)
  • RA Quinlan et al.

    Patterns of expression and organization of cytokeratin intermediate filaments

    Ann NY Acad Sci USA

    (1985)
  • T-T Sun et al.

    Monoclonal antibody studies of mammalian epithelial keratins: a review

    Ann NY Acad Sci USA

    (1985)
  • D Cooper et al.

    Classification of human epithelia and their neoplasms using monoclonal antibodies to keratins: strategies, applications, and limitations

    Lab Invest

    (1985)
  • KH Kim et al.

    Tissue specificity of epithelial keratins: differential expression of mRNAs from two multigene families

    Mol Cell Biol

    (1983)
  • R Eichner et al.

    The role of keratin subfamiles and keratin pairs in the formation of human epidermal intermediate filaments

    J Cell Biol

    (1986)
  • J Taylor-Papadimitriou et al.

    Keratin expression in the mammary gland

  • A Draeger et al.

    Cytokeratins, smooth muscle actin and vimentin in human normal salivary gland and pleomorphic adenomas. Immunocytochemical studies with particular reference to myoepithelial and basal cells

    APMIS

    (1991)
  • PM Steinert et al.

    Structural and functional implications of amino acid sequences of keratin intermediate filament subunits

  • JK Pienta et al.

    Cancer as a disease of DNA organization and dynamic cell structure

    Cancer Res

    (1989)
  • EB Lane et al.

    Use of keratin antibodies in tumor diagnosis

    Cancer Biol

    (1990)
  • PA Coulombe et al.

    A function for keratins and a common threat among different types of epidermolysis bullosa simplex diseases

    J Cell Biol

    (1991)
  • EB Lane et al.

    A mutation in the conserved helix termination peptide of keratin 5 in hereditary skin blistering

    Nature

    (1992)
  • TS Stappenbeck et al.

    The desmoplakin carboxyl terminus coaligns with and specifically disrupts intermediate filament networks when expressed in cultured cells

    J Cell Biol

    (1992)
  • H Clausen et al.

    Keratin proteins in human oral mucosa

    J Oral Pathol

    (1986)
  • PR Morgan et al.

    Site variation of keratin expression in human oral epithelia—an immunocytochemical study of individual keratins

    Epithelia

    (1987)
  • MH Sawaf et al.

    Cytokeratin profiles in oral epithelia. A review and a new classification

    J Biol Buccale

    (1991)
  • VE Gould et al.

    Neuroendocrine (Merkel) cells of the skin: hyperlasias, dysplasias, and neoplasms

    Lab Invest

    (1985)
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