Systematic Immunohistochemical Analysis of the Expression of CD46, CD55, and CD59 in Colon Cancer

Abstract

Context.-The expression of membrane-bound complement regulatory proteins (mCRPs) that inhibit the complement system in normal tissues is essential for selfprotection against an autologous immune reaction. However, the expression patterns of mCRPs, including CD46, CD55, and CD59, are inconsistent in different types of cancer cells.Objectives.-To determine whether CD46, CD55, and CD59 are differentially expressed in neoplastic and adjacent normal colon tissues and to assess their clinical significance.Design.-Immunohistochemistry was performed on tissue microarrays of cancerous and adjacent normal colon tissues.Results.-The expression levels of CD46, CD55, and CD59 were significantly higher in colon cancer tissues compared with the normal adjacent colon tissues. We found that the expression levels of CD55 and CD59 correlated with the grade of differentiation in colon cancers. In addition, the expression of CD55 and CD59 was greater in stage III and stage IV colon cancers than in stage I and stage II cancers according to staging by the TNM classification.Conclusions.-CD46, CD55, and CD59 are up-regulated in colon cancer. Specifically, CD55 and CD59 are of clinical relevance to differentiation and TNM staging of colon cancer. These data suggest that CD46, CD55, and CD59 have the potential to be used for molecular staging diagnoses and for colon cancer therapies.(Arch Pathol Lab Med. 2014;138:910-919; doi: 10.5858/ arpa.2013-0064-OA) I mmunotherapies using monoclonal antibodies (mAbs) have attracted great attention from oncologists because these mAbs can be used to directly or indirectly damage tumor cells, while sparing normal, healthy cells. In addition, complement activation by mAbs can mediate direct tumor cell lysis or antibody-dependent cell-mediated cytotoxicity. Specifically, complement activation results in the formation of C3-convertase and C5-convertase, and the cleavage of C3 leads to the generation of C3b, which attaches to the cell surface and causes amplification of the complement cascade. Cleavage of C5 by C5-convertase results in fragmentation of C5 into C5a and C5b, C5b could form a complex with C6 and C7 at the membrane surface (C5b-7 complex), and C5b-7 complex binds C8abc to form the C5b-8 complex, which ultimately binds sequentially to multiple copies of C9 to form the mature membrane attack complex. The membrane attack complex then leads to direct complement-dependent cytotoxicity (CDC) through the formation of membranepenetrating pores.1 Because the targeting of cells by CDC is destructive and irreversible, complement activation is tightly regulated by complement regulatory proteins (CRPs) to avoid uncontrolled activation and an autologous immune reaction. Complement regulatory proteins exist as soluble proteins or as membrane-bound CRPs (mCRPs). The mCRPs include mainly CD46, CD55, and CD59. Also called membrane cofactor protein (MCP), CD46 is the cofactor for factor I-mediated degradation of C3b and C4b, which prevents the continuous formation of convertases. Decayaccelerating factor, also k...

Efficacy of CD46-targeting chimeric Ad5/35 adenoviral gene therapy for colorectal cancers

“…Elevated expression of CD46 has been observed in medulloblastomas, breast cancers, and CRCs [30–32]. Although the expression level of CD46 was significantly higher in CRC tissues compared with the adjacent normal colon tissues, CD46 expression was not associated with colon cancer progression [31]. Due to the on hand availability of CRC tissues and to difficulties in evaluating the notoriously heterogeneous population of PCa, we limited our further studies to CRC.…”

Mutations in human genes that increase the risk for severe influenza infection

“…As was established by experiments in vitro, the infection of cells by the influenza virus A(H1N1)pdm09 causes the intensification of the protein CD55 expression. Patients with T/T rs2564978 genotype contain much less of CD55 on the surface of mononuclears of peripheral blood as compared with the patients with C/C and C/T genotypes [51].…”

Effect of IL-6 and IL-8 on the expression of the complement activation inhibitors MAC-inhibitory protein and decay-accelerating factor in ovarian cancer A2780 cells

“…However, to the best of our knowledge, the role of IL-6 and IL-8 on CD55 and CD59 expression in ovarian cancer cells has not yet been characterized and investigated. Shang et al (7) demonstrated that the expression levels of CD46, CD55 and CD59 were significantly higher in colon cancer tissues compared with normal colon tissues. However, this was independent of the presence of IL-6 and IL-8.…”

“…An increase in CD55 and CD59 expression has also been associated with a poor response to treatment, an increased tumour stage and shorter disease-free survival time of patients (4)(5)(6)(7). Consequently, the activity of complement inhibitors CD59 and CD55 may be associated with the mechanism of cancer cell escape (3).…”