Cytokeratin Immunoreactivity in Lobular Intraepithelial Neoplasia

Abstract

S U M M A R Y Eighteen commercially available antibodies reactive against different cytokeratin proteins were tested on classic examples of lobular intraepithelial neoplasia (LIN) and of ductal intraepithelial neoplasia (DIN) of the breast. About 90% of higher-grade DIN (AIDH and DCIS) show no or substantially diminished reaction with clone 34 ␤ E12 (specified as reactive against keratins 1, 5, 10, and 14 as determined by the manufacturer), while the cells of LIN were found to express the antigen reactive with this antibody. To determine which of these four keratins are present in the cells of LIN, antibodies reactive against these individual four keratins were tested. None of the four antibodies to keratins 1, 5, 10, or 14 reacted with the cells of LIN. To investigate this further, 13 additional monoclonal antibodies to various other keratin proteins were tested on the cells of LIN. Those that successfully reacted with the cells of LIN were further tested on the cells of DIN. All of the individual antibodies reactive with the cells of LIN were also reactive with the cells of DIN to a degree, with clone RCK108 (reactive against keratin 19) coming the closest to demonstrating the reactivity seen with 34 ␤ E12. We conclude that the reactivity seen in the cells of LIN with 34 ␤ E12 is due to either (a) a crossreaction with keratin 19 that is slightly less prominent than the reaction of the individual clone RCK108, (b) a crossreaction with a keratin protein that was not tested (3, 11, 12), (c) a crossreaction with a protein closely resembling keratin in formalin-fixed, paraffin-embedded tissue, or (d) the detection of a mutated or truncated form of keratin 1, 5, 10, or 14 that cannot be detected by the individual monoclonal antibody. L obular intraepithelial neoplasia (LIN) is a disease of the breast that increases the risk for breast cancer in those afflicted (Tavassoli 1999). LIN cells are usually characterized by a lack of E-cadherin protein along with the presence of a high molecular weight cytokeratin as demonstrated by immunohistochemistry (IHC) with the commonly used antibody clone 34 ␤ E12 (Bratthauer et al. 2002). Available worldwide and in use for 20 years, clone 34 ␤ E12 is believed to be reactive against keratin proteins 1, 5, 10, and 14, according to the manufacturer (Gown and Vogel 1982). This antibody shows a perinuclear, often polarized immunoreactivity in every LIN we have evaluated, 40 of which have been reported on (Bratthauer et al. 2002) and in an additional 20 cases studied since.This study was designed to determine which of the four keratin proteins identified by 34 ␤ E12 were detected in the cells of LIN.To that end, we tested individual antibodies reactive against keratins 1, 5, 10, and 14 on classic LIN. To our surprise, none of these reacted with the cells of LIN. We then obtained monoclonal antibodies (MAbs) to an additional 13 keratin proteins to determine if there was a previously unrecognized or undetected crossreaction of 34 ␤ E12 with another keratin protein in formalin-fixed, paraff...

Basal Phenotype in Breast Carcinoma Occurring in Women Aged 35 or Younger

“…However, it was found to give a positive staining in some non-basal carcinomas too, resulting in a sensitivity of 81% and a specificity of 87%. Likewise, lobular neoplasia was reported to stain positively with this antibody despite reacting with any of the antibodies against the specific cytokeratin components [31]. Nevertheless, in this series, the lack of HMWCK staining had a 94% negative predictive value as concerns the basal-like phenotype.…”

Expression of membrane type-1 matrix metalloproteinase, MT1-MMP in human breast cancer and its impact on invasiveness of breast cancer cells

“…This relatively stable cytoskeletal associated protein has been widely used as a marker of cancer cells in tissues other than mammary gland, such as lymph nodes and bone marrow and has been valuable in identifying the metastatic cells in these tissues (35,36). The marker is not only useful in identifying cancer cells, it has been recognised as an epithelial marker.…”

Significance of immunohistochemistry in breast cancer

“…The majority of ductal carcinomas express cytoplasmic E-cadherin, whereas most lobular carcinomas lack expression of E-cadherin [3,15,16] . In addition, the differences in CKs expression may be used: highmolecular-weight CK (clone 34βE12) is usually expressed by lobular carcinomas, but is absent or expressed at low levels in most cases of DCIS [3,17,18] . In the same context, CK 8 is stained in ductal carcinoma cells in the peripheral cytoplasm, while perinuclear staining is characteristic of lobular carcinoma [19] .…”