Advantages of CK 5 & 14

The detection of PIN (prostate intraepithelial neoplasia) involves distinguishing the neoplastic tissue in prostate biopsies (commonly detected with the P504s/Racemase antibody) from the benign glandular tissue (commonly detected with a high molecular weight cytokeratin or p63 antibody). Historically, the most commonly used high molecular weight keratin for labeling benign prostate glands has been Cytokeratin 34betaE12, also known as Cytokeratin 903. This can possibly be attributed to Cytokeratin 34betaE12 being one of the earliest and most widely published clones to be cited for use in labeling benign prostate myoepithelial cells.

However, recent findings have suggested that the use of different high molecular weight keratins are preferred over CK34betaE12 due to consistency and higher sensitivity in labeling benign prostate glands. Inconsistency of CK34betaE12 may be attributed to fixation protocol differences, as literature cites that staining is inversely proportional to fixation time.2 CK34betaE12 showed only a 40% sensitivity of staining benign glands in another study comparing it with Cytokeratin 5/6.3 This evidence shows that while CK34betaE12 has been the most commonly used marker for prostate glandular epithelium labeling, it is far from the best.

High molecular weight cytokeratins 5 and 14 are expressed as a pair in basal cells of stratified epithelia, where they occur as bundled arrays of filaments. When combined, these two keratins show a much higher sensivity towards benign prostate myoepithelial cells than CK34betaE12, as well as a much higher sensitivity towards 'basal' epithelium in the breast than cytokeratin 5/6. This may be explained by the lack of evidence for CK6 messenger RNA expression in normal breast and basal-like carcinomas.

This evidence, in addition to the superior staining of CK5/14 in comparison to CK5/6 and CK34betaE12, supports using Cytokeratin 5/14 routinely for both prostate and breast myoepithelial cell identification as a preferred alternative to CK34betaE12 and CK5/6.

Literature:

1. Hedrick L, Epstein JI. Use of keratin 903 as an adjunct in the diagnosis of prostate carcinoma. Am J Surg Pathol. 1989 May;13(5):389- 96.

2. Hammed O, Humphrey PA. Immunohistochemistry in the diagnosis of minimal prostate cancer. Current Diagnostic Pathology 2006;12:279-291

3. Abrahams NA, Ormsby AH, Brainard J. Validation of cytokeratin 5/6 as an effective substitute for keratin 903 in the differentiation of benign from malignant glands in prostate needle biopsies. Histopathology. 2002 Jul;41(1):35-41.

4. Bousquet O, Ma L, Yamada S, Gu C, Idei T, Takahashi K, Wirtz D, Coulombe PA. The nonhelical tail domain of keratin 14 promotes filament bundling and enhances the mechanical properties of keratin intermediate filaments in vitro. J Cell Biol. 2001 Nov 26;155(5):747-54.

5. Bhargava R, Beriwal S, McManus K, Dabbs DJ. CK5 is more sensitive than CK5/6 in identifying the "basal-like" phenotype of breast carcinoma. Am J Clin Pathol. 2008 Nov;130(5):724-30.

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