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Journal of Clinical Pathology logoLink to Journal of Clinical Pathology
. 2001 Dec;54(12):927–932. doi: 10.1136/jcp.54.12.927

The expression of antiapoptotic proteins Bcl-2, Bcl-XL, and Mcl-1 in benign, dysplastic, and malignant biliary epithelium

A Okaro 1, A Deery 1, R Hutchins 1, B Davidson 1
PMCID: PMC1731328  PMID: 11729212

Abstract

Aim—Cholangiocarcinoma can be cured by surgery, but only in a minority of cases. The activation of apoptosis is a major mode of action of chemotherapy and radiotherapy, which have limited benefit in the treatment of cholangiocarcinoma. The antiapoptotic members of the Bcl-2 protein family (Bcl-2, Bcl-XL, and Mcl-1) are important inhibitors of apoptosis, but have not been investigated extensively in cholangiocarcinoma.

Methods—The expression of Bcl-2, Bcl-XL, and Mcl-1 was investigated in normal biliary epithelium (17), biliary dysplasia (three), and invasive cholangiocarcinoma (51), in addition to three human cholangiocarcinoma cell lines, by immunohistochemistry and immunofluorescence.

Results—The expression of Bcl-2 was not detected in normal or malignant biliary tissue. In contrast, granular cytoplasmic Bcl-XL and Mcl-1 staining was found in 60–100% of cells in all normal, dysplastic, and malignant specimens, including the human cell lines examined in this study.

Conclusion—These findings indicate that Mcl-1 and Bcl-XL, but not Bcl-2, are involved in the survival of normal and neoplastic cells in the biliary tree. By prolonging survival through blocking apoptosis, these proteins might be reducing the efficacy of cytotoxic anticancer treatments in cholangiocarcinoma.

Key Words: cholangiocarcinoma • apoptosis • Bcl-2 • Mcl-2 • Bcl-XL

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Figure 1 Bcl-2 protein expression in biliary epithelial cells. (A) The human cholangiocarcinoma cell line Egi-1 does not express Bcl-2. (B) Normal bile duct brush cytology cells stain negative for Bcl-2. (C) Cholangiocarcinoma cells located in the desmoplastic reaction (arrow) and within a lymph node (arrowhead) do not express Bcl-2. Positive Bcl-2 staining is clearly demonstrated in the internal positive control (lymph node). (D) Positive Bcl-2 staining is shown in cells of regenerating bile ductules.

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Figure 2 (A,C) Haematoxylin and eosin stain of cholangiocarcinoma. (B) Bcl-XL expression in cholangiocarcinoma. (D) Cholangiocarcinoma cells within a lymph node express Mcl-1; note the granular cytoplasmic pattern of staining for the Bcl-XL and Mcl-1 proteins.

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Figure 3 (A) Normal brush cytology cells and (B) the human cell line Tfk-1 also express Bcl-XL. Immunofluorescence images show (C) the Bcl-XL and (D) Mcl-1 proteins in Egi-1 localise to intracellular organelles, such as the mitochondria.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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