34βE12

WP

Definition: 34βE12 is an antibody specific for high molecular weight cytokeratins CK1, CK5, CK10 and CK14. It is sometimes, less precisely, referred to as high-molecular weight keratin (HMWK) and high-molecular weight cytokeratin (HMWCK).

Immunoreactivity

The prostatic secretory cells and prostatic basal cells are immunoreactive for antibodies to broad spectrum and low molecular weight cytokeratins. However, only basal cells express high molecular weight cytokeratins.

One high molecular monoclonal cytokeratin antibody, clone 34βE12, recognizes 57 and 66 kilodalton cytokeratins in stratum corneum corresponding to Moll numbers 1, 5, 10 and 14, and is widely used as a basal cell specific marker active in paraffin-embedded tissue following proteolytic digestion.

34βE12 is also immunoreactive against squamous, urothelial, bronchial/pneumocyte, thymic, some intestinal and ductal epithelium (breast, pancreas, bile duct, salivary gland, sweat duct, renal collecting duct), and mesothelium.

An immunoperoxidase cocktail containing monoclonal antibodies to cytokeratins 5 and 6 is also an effective basal cell stain.

Diagnostic use

 prostate

• 34βE12 is used to stain basal cells in prostatic glands; loss of basal cells is seen in prostate adenocarcinoma (the most common form of prostate cancer).
• Since uniform absence of a basal cell layer in prostatic acinar proliferations is one important diagnostic feature of invasive carcinoma and basal cells may be inapparent by H&E stain, basal cell specific immunostains may help to distinguish invasive prostatic adenocarcinoma from benign small acinar cancer - mimics which retain their basal cell layer, e.g. glandular atrophy, post-atrophic hyperplasia, adenosis (atypical adenomatous hyperplasia), sclerosing adenosis and radiation induced atypia.
• Because the basal cell layer may be interrupted or not demonstrable in small numbers of benign glands, the complete absence of a basal cell layer in a small focus of acini cannot be used alone as a definitive criterion for malignancy.
• Rather, absence of a basal cell layer is supportive of invasive carcinoma only in acinar proliferations which exhibit suspicious cytologic and / or architectural features on H&E stain.
• Conversely, some early invasive prostatic carcinomas, e.g. microinvasive carcinomas arising in association with or independent of high grade prostatic intraepithelial neoplasia, may have residual basal cells.
• Intraductal spread of invasive carcinoma and entrapped benign glands are other proposed explanations for residual basal cells.
• Rare prostatic adenocarcinomas contain sparse neoplastic glandular cells, which are immunoreactive for 34βE12, yet these are not in a basal cell distribution.
• The use of antibodies for 34βE12 is especially helpful for the diagnosis for of deceptively benign appearing variants of prostate cancer.
• Immunohistochemistry for cytokeratin-7 CK7 and cytokeratin-20 CK20 have a limited diagnostic use in prostate pathology with the exception that negative staining for both markers, which can occur in prostate adenocarcinoma, would be unusual for transitional cell carcinoma.

 Breast cancer

• It can be used to differentiate in situ cancers of the breast; lobular carcinoma in situ (LCIS) exhibits perinuclear staining with 34βE12. Ductal carcinoma in situ (DCIS) does not stain for 34βE12.
• p63 and 34βE12 in fine needle aspiration cytology specimens for breast lesion are potentially useful discriminatory markers between intraductal papilloma and ductal carcinoma in situ.
• The immunostaining of FNA breast specimens for p63 and 34βE12 may help in difficult diagnoses. doi : 10.1111/cyt.12244

References

 Aishima S, Asayama Y, Taguchi K, et al. (November 2002). "The utility of keratin 903 as a new prognostic marker in mass-forming-type intrahepatic cholangiocarcinoma". Mod. Pathol. 15 (11): 1181–90. doi : 10.1097/01.MP.0000032537.82380.69 PMID 12429797.

 Yeh IT, Mies C (March 2008). "Application of immunohistochemistry to breast lesions". Arch. Pathol. Lab. Med. 132 (3): 349–58. doi : 10.1043/1543-2165(2008)132[349:AOITBL]2.0.CO;2 PMID 18318578.