34bE12, anti-cytokeratin K903 34bE12

This monoclonal mouse antibody reacts with cytokeratins 1, 5, 10 and 145. 903 is the catalogue number. Immunoreactivity in formalin-fixed, paraffin-embedded tissue requires antigen retrieval. Use proteolytic treatment for prostatic tissue and microwave antigen retrieval with overnight incubation of the primary antibody at 4°C for thyroid tissue1.

Immunohistochemical expression

normal squamous, ductal and other complex epithelia
In the lung, bronchial basal and parabasal cells and some vertically orientated non-mucinous cells5. Squamous cell carcinoma, including lung and including basaloid variant of squamous cell carcinoma of the lung2 and basaloid cell carcinoma of the lung2. There is slight staining of myoepithelial cells and of cuboidal and columnar cells of bronchial ducts.5 Bronchiolar basal cells stain, whereas Clara cells and type I and II pneumocytes are unstained5. Neuroendocrine hyperplasia and tumourlets are negative5.
ductal carcinoma of breast, pancreas, bile duct and salivary gland
transitional cell carcinoma of bladder
nasopharyngeal carcinoma
thymoma
epithelioid mesothelioma

It is negative in:

hepatocellular carcinoma
renal cell carcinoma
endometrioid carcinoma
neuroendocrine tumours of lung

Diagnostic utility

34bE12 reacts with the basal cells in benign prostatic acini, including basal cell hyperplasia and atypical adenomatous hyperplasia7, but not with prostatic adenocarcinoma1,8. Staining may occur in some prostatic carcinomas13, particularly high-grade carcinomas (Gleason score at least 7)10. There are rare prostatic carcinomas in which there appear to be residual basal cells, positive for both 34bE12 and p6311,12.

Staining is patchy in benign glands and only the complete absence of basal cell staining in all glands in a particular focus of concern should be taken as evidence of carcinoma14. CK5/6 may be superior, particularly when Hollandes fixative is used, although the paper that made this claim used proteolytic digestion for 34bE12 and heat-induced antigen retrieval for CK5/64. One study found that 11% of normal glands and 40% of atrophic glands had a discontinuous pattern of staining3. Since the intensity of staining varies for technical reasons, adjacent benign gland should be used as an internal control6. There is progressive loss of staining with prolonged fixation, which may be retrieved by the heat-induced (hot plate) method of antigen retrieval, which is superior to enzymatic pretreatment14, although this may also cause weak staining of malignant glands9. 34bE12 is useful in conjunction with P504S, which shows a complementary positivity in prostatic adenocarcinoma. It may be somewhat inferior to p63 and a cocktail of 34bE12 and p63 may be superior to either alone.

reacts with papillary carcinoma, but not (or only focally) with hyperplastic thyroid nodules or follicular carcinoma1.
Exclusion of neuroendocrine differentiation in lung tumours.
differentiation of ductal from lobular mammary intra-epithelial neoplasia.

References

1Leong A S-Y, Cooper K and Leong FJ W-M. Manual of diagnostic antibodies for immunohistology. Oxford University Press. ISBN 1 900 151 316. Published 1999.

2Sturm, N., Lantuejoul, S., Laverriere, M. H., Papotti, M., Brichon, P. Y., Brambilla, C., Brambilla, E. Thyroid transcription factor 1 and cytokeratins 1, 5, 10, 14 (34betaE12) expression in basaloid and large-cell neuroendocrine carcinomas of the lung. Hum Pathol 2001;32:918-925.

3Hedrick, L. and Epstein, J.I. Use of keratin 903 as an adjunct in the diagnosis of prostate carcinoma. Am J Surg Pathol 1989;13:389-96.

4Abrahams, N.A., Ormsby, A.H. and 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;41:35-41.

5Sturm, N., Rossi, G., Lantuejoul, S., Laverriere, M.H., Papotti, M., Brichon, P.Y., Brambilla, C. and Brambilla, E. 34betaE12 expression along the whole spectrum of neuroendocrine proliferations of the lung, from neuroendocrine cell hyperplasia to small cell carcinoma. Histopathology 2003;42:156-166.

6Magi-Galluzzi, C., J. Luo, et al. (2003). "Alpha-methylacyl-CoA racemase: a variably sensitive immunohistochemical marker for the diagnosis of small prostate cancer foci on needle biopsy." Am J Surg Pathol 27(8): 1128-33.

7Yang, X. J., C. L. Wu, et al. (2002). "Expression of alpha-Methylacyl-CoA racemase (P504S) in atypical adenomatous hyperplasia of the prostate." Am J Surg Pathol 26(7): 921-5.

8Wojno, K. J. and J. I. Epstein (1995). "The utility of basal cell-specific anti-cytokeratin antibody (34 beta E12) in the diagnosis of prostate cancer. A review of 228 cases." Am J Surg Pathol 19(3): 251-60.

9Varma, M., M. D. Linden, et al. (1999). "Effect of formalin fixation and epitope retrieval techniques on antibody 34betaE12 immunostaining of prostatic tissues." Mod Pathol 12(5): 472-8.

10Googe, P. B., K. M. McGinley, et al. (1997). "Anticytokeratin antibody 34 beta E12 staining in prostate carcinoma." Am J Clin Pathol 107(2): 219-23.

11Oliai, B. R., H. Kahane, et al. (2002). "Can basal cells be seen in adenocarcinoma of the prostate?: an immunohistochemical study using high molecular weight cytokeratin (clone 34betaE12) antibody." Am J Surg Pathol 26(9): 1151-60.

12Shah, I. A., M. O. Schlageter, et al. (1991). "Cytokeratin immunohistochemistry as a diagnostic tool for distinguishing malignant from benign epithelial lesions of the prostate." Mod Pathol 4(2): 220-4.

13Yang, X. J., K. Lecksell, et al. (1999). "Rare expression of high-molecular-weight cytokeratin in adenocarcinoma of the prostate gland: a study of 100 cases of metastatic and locally advanced prostate cancer." Am J Surg Pathol 23(2): 147-52.

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

This page last revised 21.9.2006.