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 adenocarcinoma^1,8. 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 p63^11,12.

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.

©SMUHT/PW Bishop