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Cytokeratins in the detection of tumors

Cytokeratins (CKs, or following more recent nomenclature also simply called keratins) are intermediate filament?forming proteins that provide mechanical support and fulfill a variety of additional functions in epithelial cells. They are part of the cytoskeleton and the largest family of intermediate filament proteins. Two types of Cytokeratins are distinguished that form heterodimers, namely acidic type I (Cytokeratins 9-23) and basic type II (Cytokeratins 1-8).

The specific nature of these heterodimers serves to distinguish different epithelial cells, in which they are expressed, and has also become important in the classification of tumor cells. Mutations in most of them are now associated with specific tissue-fragility disorders, and antibodies to Cytokeratins are important markers of tissue differentiation.

Importantly, they are tools in diagnostic pathology, most importantly in the detection of tumors. Primary tumors and metastases of a given carcinoma share the same pattern of cytokeratins, that distinguishes them from other types of carcinomas, thereby allowing differentiation between the different tumors (Ref. 1-4).

For example, Mesotheliomas (a protective lining that covers most of the body's internal organs) and Adenocarcinomas (originating in glandular tissue) can be distinguished by detection of . Defects in lead to inherited skin disorders such as epidermolysis bullosa simplex (EBS) or Dowling-Deogs disease (DDD) (Ref. 5-7).

can be used as a tool in order to distinguish ovarian and gastrointestinal carcinomas, or transitional cell carcinomas and prostate . In hepatocytes atypical expression of is a marker for primary biliary cirrhosis (Ref. 8-10).

and have a structural role in simple epithelia. Additionally, they play a role in signaling that modulates cell attachment, protein synthesis, G1/S phase transition, and in stress adaptation. Furthermore, can be applied to detect therapy-induced tumor apoptosis and necrosis (Ref. 11-14).

Squamous cell (that have protective functions to nutrition exchange) carcinomas can be diagnosed utilizing , and as biomarkers.

Because is being speculated to be linked to the retention of an undifferentiated cell character it may be useful in the detection of a variety of tumors (Ref 18-22).

Below we have compiled a list that is intended to help you find what you need in your research:

Carcinoma Cytokeratins Selected antibodies
Hepatocellular carcinoma 8, 18 Cytokeratin 8
Adenocarcinoma of colon, type 1 8, 18, 19 Cytokeratin 18
Adenocarcinoma of colon, type 2 8, 17, 18, 19 Cytokeratin 17
Adenocarcinoma of stomach 7, 8, 18, 19 Cytokeratin 7, 17
Adenocarcinoma of esophagus 8, 18, 19 Cytokeratin 19
Adenocarcinoma of pancreas 7, 8, 17, 18, 19 Cytokeratin 18
Ductal (adeno-) carcinoma of breast, type 1 7, 8, 18, 19 Cytokeratin 19
Basal cell epithelioma 5, 6, 8, 14, 15, 17 Cytokeratin 5, 18
Squamous cell carcinoma of skin 5, 6, 11, 14, 16, 17 Cytokeratin pan
Squamous cell carcinoma of tongue 5, 6, 14, 16, 17 Cytokeratin 14
Ductal carcinoma of breast, type 2 6, 7, 8, 11, 14, 16, 17, 18, 19 Cytokeratin 18
Undifferentiated carcinoma of bronchus (large-cell type) 6, 7, 8, 17, 18, 19 Cytokeratin 18
Solid carcinoma of maxillary sinus 5, 8, 17, 18, 19 Cytokeratin 17
Adamantinoma 4, 5, 8, 14, 15, 16, 17, 19 Cytokeratin 19
Squamous cell carcinoma of epiglottis 4, 5, 6, 8, 14, 15, 16, 17, 18, 19 Cytokeratin 18
Squamous cell carcinoma of esophagus 4, 5, 8, 14, 15, 16, 17, 19 Cytokeratin 14
Squamous cell carcinoma of rectal-anal region 4, 5, 6, 8, 10, 11, 14, 15, 16, 17, 18, 19 Cytokeratin 10
Cloacogenic carcinoma 1, 5, 6, 7, 8, 10, 11, 13, 14, 15, 17, 19 Cytokeratin 10, 13
Source: Moll R. et al; Cell 1982; 31: 11-24 (1). Varadhachary G.R. et al.; Cancer 2004; 100: 1776-1785 (2). Gusterson B.A. et al.; Breast Cancer Res. 2005; 7: 143-148 (3). Kanaji N. et al.; Lung Cancer 2007; 55: 295-302 (4). Moll R. et al.; Virchows Arch. B Cell Pathol. Incl. Mol. Pathol. 1989; 58: 129-145 (5). Rugg E.L. et al.; J. Invest. Dermatol. 2007; 127: 574-580 (6). Betz R.C. et al.; Am. J. Human Genet. 2006; 78: 510-519 (7). Ramaekers F. et al.; Am. J. Pathol. 1990; 136: 641-655 (8). Yabushita K. et al.; Liver 2001; 21: 50-55 (9). Chatzipantelis P. et al.; Hepatol. Res. 2006; 36: 182-187 (10). Galarneau L. et al.; Exp. Cell Res. 2007; 313: 179-194 (11). Ku N.-O. and Omary M.B.; J. Cell Biol. 2006; 174: 115-125 (12). Lau A.T. and Chiu J.F.; Cancer Res. 2007; 67: 2107-2113 (13). Linder S. et al; Cancer Lett. 2004; 214: 1-9 (14). van Dorst E.B.L. et al.; J. Clin. Pathol. 1998; 51: 679-684 (15). Maddox P. et al.; J. Clin. Pathol. 1999; 52: 41-46 (16). Toyoshima T. et al.; J. Cancer Res. Clin. Oncol. 2008; 134: 515-521 (17). Deshpande V. et al.; Am. J. Surg. Pathol. 2004; 28: 1145-1153 (18). Park Y.J. et al.; J. Korean Med. Sci. 2007; 22: 621-628 (19). Barroeta J.E. et al; Endocr. Pathol. 2006; 17: 225-234 (20). Ignatiadis M. et al.; J. Clin. Oncol. 2007; [Epub ahead of print] (21). Lindberg K. and Rheinwald J.G.; Am. J. Pathol. 1989; 134: 89-98 (22).
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