Keratins cytokeratins

Keratins are alpha-type fibrous polypeptides with a diameter of 7 11 nm. They are important components of the cytoskeleton in almost all epithelial cells as well as in some nonepithelial cell types. Keratins are generally held to be the most ubiquitous markers of epithelial differentiation. So far, 20 distinct types numbered by Moll et al. (1982a, 1990, 1992) have been revealed. Keratins were earlier thought to be separable into hard and soft, or cytokeratins and other keratins, but these designations are now understood to be incorrect. In 2006, a new nomenclature (Schweizer et al. 2006) was adopted for describing keratins which takes this into account (Table 13.1). 

Chu PG, Weiss LM (2002a) Expression of cytokeratin 5/6 in epithelial neoplasms an immuno histochemical study of 509 cases. Mod Pathol 15(1) 6 10 Chu PG, Weiss LM (2002b) Keratin expression in human tissues and neoplasms. Histopathology 40(5) 403 439... 

Moll R, Franke WW, Vole Platzer B, Krepler R (1982b) Different keratin polypeptides in epider mis and other epithelia of human skin a specific cytokeratin of molecular weight 46,000 in epithelia of the pilosebaceous tract and basal cell epitheliomas. J Cell Biol 95(1) 285 295 Moll R, Krepler R, Franke WW (1983) Complex cytokeratin polypeptide patterns observed in certain human carcinomas. Differentiation 23(3) 256 269 Moll R, Dhouailly D, Sun TT (1989) 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 58(2) 129 145 Moll R, Schiller DL, Franke WW (1990) Identification of protein IT of the intestinal cytoskeleton as a novel type I cytokeratin with unusual properties and expression patterns. J Cell Biol 111(2) 567 580... 

Moll R, Lowe A, Laufer J, Franke WW (1992) Cytokeratin 20 in human carcinomas. A new histodiagnostic marker detected by monoclonal antibodies. Am J Pathol 140 427 447 Moll R, Divo M, Langbein L (2008) The human keratins biology and pathology. Histochem Cell Biol 129 705 733... 

The components of the intermediate filaments belong to five related protein families. They are specific for particular cell types. Typical representatives include the cytokeratins, desmin, vimentin, glial fibrillary acidic protein (GFAP), and neurofilament. These proteins all have a rod-shaped basic structure in the center, which is known as a superhelix ( coiled coil see keratin, p. 70). The dimers are arranged in an antiparallel fashion to form tet-ramers. A staggered head-to-head arrangement produces protofilaments. Eight protofilaments ultimately form an intermediary filament. 

Especially focal keratinizing metaplasia, as it may occur after a vitamin A deficiency, is sfrengfhening the assumption of an impairmenf of the differentiation on the level of the gene expression. Since vitamin A regulates the expression of different cytokeratins and therefore influences... 

Abnormal tissues The antibody labeled 17/20 sarcomas, 16/18 melanomas, 4/4 meningeomas, and 3/3 schwannomas, and was the sole intermediate filament present in these tumours. In addition, variable percentages (10 to 57 percent) of carcinomas, neuroendocrine carcinomas, neuroblastomas, thymomas and mesotheliomas were positive with the antibody. With the exception of the neuroblastomas, cytokeratin was coexpressed with vimentin in these tumours. Among adenocarcinomas, more than 50 percent of papillary carcinomas of the thyroid as well as renal, endometrial, ovarian and lung carcinomas were labeled by the antibody and coexpressed keratins and vimentin. 

Cytokeratin Intermediate filament keratins found in epithelial tissue. There are two types of cytokeratins the acidic type 1 cytokeratins and the basic or neutral type 11 cytokeratins. Cytokeratins are thought to play a role in the activation of plasma prekallikrein and plasminogen. See Crewther, W.G., Fraser, R.D., Lennox, F.G., and Lindley, H., The chemistry of keratins, Adv. Protein Chem. 20, 191-346, 1965 Masri, M.S. and Friedman, M., Interactions of keratins with metal ions uptake profiles, mode of binding, and effects on the properties of wool, Arfv. Exp. Med. Biol. 48, 551-587,1974 Fuchs, E. and Green, H., Multiple keratins of cultured human epidermal cells are translated from different mRNA molecules. Cell 17, 573-582, 1979 ... 

B. A., Ross, D.T., Heath, V.J., and Stein, T Basal cytokeratins and their relationship to the cellular origin and functional classification of breast cancer, Breast Cancer Res. 1, 143-148, 2005 Skakle, J., Applications of X-ray powder diffraction in materials chemistry, Chem. Rec. 5, 252-262, 2005. See also Keratin. 

Five classes of intermediate filament proteins have been described, generally referred to as types I through V. Types I and II are the acidic and basic polypeptides, respectively, which comprise the keratins and cytokeratins, a family of heteropolymers that are abundant in epithelia. Type III consist of vimentin, desmin, glial fibrillary acidic protein, and peripherin. Of these, desmin has specific importance... 

Typical ES/PNET is nonreactive for chromogranin, cytokeratin, glial fibrillary protein, desmin, muscle-specific actin, myogenin, CD31, and However, in studies of tumors that were confirmed by molecular identification of the t(ll 22) translocation, immunoreactivity for cytokeratin has been present in 20% to 30% of ES/PNET cases.Nonetheless, in our experience, keratin has been relatively focally expressed in these tumors when present. NB84 (a marker developed for recognition of neuroblastoma) is also apparent in roughly 20% of ES/PNETs. 

A consistent immunophenotypic attribute of epithelioid sarcoma is an intense perinuclear zone of vimentin and keratin reactivity (Fig. 4.20). It is attributable to perinuclear collections of intermediate filaments that are seen at an ultrastructural level. The scope of cytokeratin labeling may be heterogeneous in any given tumor (Fig. 

Jiang J, Ulbright TM, Younger C, et al. Cytokeratin 7 and cyto-keratin 20 in primary urinary bladder carcinoma and matched lymph node metastasis. Arch Pathol Lab Med. 2001 125 921-923. 

Conventional SCC usually has fairly diagnostic histologic features, and in well-differentiated tumors no additional stains are generally necessary. In poorly differentiated tumors, particularly in metastatic sites, cytokeratin stains may be helpful. Typically, head and neck SCCs are positive for cytokeratin cocktails, AEl-3, and pancytokeratin. Cytoplasmic expression of keratins CK5, CK5/6, CK14, and CK17 are also frequently found in SCCs, along with nuclear p63 expression. 

From Franchi A, Moroni M, Mass D, et al. Sinonasal undifferentiated carcinoma, nasopharyngeal-type undifferentiated carcinoma, and keratinizing and nonkeratinizing squamous cell carcinoma express different cytokeratin patterns. Am / Surg Pathol. 2002 26 1597-1 604. 

FIGURE 10.4 Distribution of markers in pituitary adenomas. CHR-A, chromogranin A KER (CAMS.2), keratins detected with monoclonal antibody CAMS.2 SYNAP, synaptophysin NSE, neuron-specific enolase KER (AE1/AE3), keratins detected with antibodies AE1 and AE3 HBME-1 CK7, cytokeratin 7 CK19, cytokeratin 19 CFAP, glial fibrillary acid protein. 

Sturm and colleagues evaluated TTF-1 and 34f5E12 (cytokeratins 1,5,10, and 14) expression in basaloid and large cell neuroendocrine carcinomas. The authors did not observe TTF-1 expression in basaloid carcinomas, and they observed expression of high molecular weight keratin (34(1E12) in only one large cell neuroendocrine carcinoma. Basaloid carcinoma is contrasted with small... 

CK5/CK6 D5/16B4 Keratins—Moll numbers 5, 6 (and 4—to a slight degree) Purified cytokeratin 5 Biocare Medical 1 100 HIER... 

Attanoos and associates evaluated 31 sarcomatoid mesotheliomas and a spectrum of other spindle cell neoplasms with antibodies directed against cytokeratin, thrombomodulin, calretinin, and CK5/6. Twenty-four of 31 (77%) sarcomatoid mesotheliomas expressed cytokeratin, 9 of 31 (29%) expressed thrombomodulin, 12 of 31 (39%) expressed calretinin, and 9 of 31 (29%) expressed CK5/6. Two of 9 (22%) sarcomas not otherwise specified expressed broad-spectrum cytokeratin and thrombomodulin, and 1 of 9 (11%) expressed CK5/6. As might be expected, 100% of synovial sarcomas expressed broad-spectrum keratin but showed no immu-nostaining for thrombomodulin, calretinin, and CK5/6. Two of 3 (67%) angiosarcomas expressed thrombomodulin, which is not surprising since thrombomodulin... 

These authors use a battery of antibodies to evaluate mesothelial proliferative lesions, including reactive and neoplastic processes. Keratin antibodies, with the exception of CK5/6, are generally not used to differentiate an epithelial mesothelioma from another neoplasm or from a reactive process, but are used to identify the extent of a neoplastic or reactive mesothelial cell process. The antibodies we use to differentiate a well or moderately well differentiated epithelial mesothelioma from a pulmonary adenocarcinoma or nonpulmonary adenocarcinoma include AE1/AE3 cytokeratin, CK5/6, CK7, CK20, vimentin, EMA, EIBME-1, calretinin, mesothe-lin, WTl, D2-40, caldesmon, CEA, LeuMl, B72.3, BerEP4, and TTE-1. 

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