Expression of non‐membranous β‐catenin and γ‐catenin, c‐Myc and cyclin D1 in relation to patient outcome in human colon adenocarcinomas

Abstract

Non-membranous beta-catenin and gamma-catenin, c-Myc and cyclin D1 are key participants in the Wnt cell signalling pathway, in which aberrancies have been associated with malignant cell transformation. We assessed the independent prognostic value of these proteins in a clinical material. Tumours from a series of 162 patients operated on for Dukes' stage A, B and C colonic adenocarcinomas were analysed using semiquantitative immunohistochemistry and the results were related to patient outcome. Patients expressing nuclear beta-catenin in the primary tumour showed reduced survival compared to other patients (log rank p=0.028) and there was also an association with development of metastases follow-up (logistic regression p=0.024). Using multivariate analysis (Cox regression) co-expression of nuclear beta-catenin and c-Myc turned out to be the strongest marker of impaired prognosis (p=0.001, HR 5.26, 95% CI 1.93-14.36). Expression of non-membranous gamma-catenin, cyclin D1 and c-Myc alone failed to have independent prognostic significance in our study.

Meta-analysis of Colorectal Cancer Gene Expression Profiling Studies Identifies Consistently Reported Candidate Biomarkers

“…Immunohistochemistry on MYC has shown that its expression increases during disease progression (43), and when combined with nuclear h-catenin expression, MYC expression was shown to have prognostic utility (44).…”

The knockdown of c-myc expression by RNAi inhibits cell proliferation in human colon cancer HT-29 cells in vitro and in vivo

“…The importance of c-myc expression in colon cancer has been demonstrated in both studies of transgenic mice and clinical research [10,11]. Clinical studies have also indicated that c-myc is important in the development and progression of colon cancer, since over-expression of the oncogene was found in most colon cancer patients, correlated with poor prognosis [4]. The role of c-myc in colon cancer has been extensively studied for the past decade [12], and specific reduction of its level by genetic means in colon cancer cell lines is believed to be valuable in understanding its sustained malignant phenotype.…”

“…c-myc is believed to participate in most aspects of cellular function, including replication, growth, metabolism, differentiation, and apoptosis [6][7][8]. A frequent genetic abnormality seen in colon cancer is the elevated expression of c-myc [4,9]. The importance of c-myc expression in colon cancer has been demonstrated in both studies of transgenic mice and clinical research [10,11].…”

“…In this regard, several investigations have been directed toward uncovering alterations in the gene structure, gene expression, or activity of gene products associated with this prevalent disease [2]. The members of the myc proto-oncogene family, c-, L-, and N-myc, are thought to be central regulators of cell growth, and deregulated myc expression is associated with many cancers, including colon cancer [3][4][5]. c-myc is believed to participate in most aspects of cellular function, including replication, growth, metabolism, differentiation, and apoptosis [6][7][8].…”

Helicobacter Infection Is Required for Inflammation and Colon Cancer in Smad3-Deficient Mice

“…In humans, c-myc is overexpressed in most colon cancers, and coexpression of c-myc and h-catenin are associated with markedly reduced patient survival (51). Genetic polymorphisms in both IL-1 and TNF-a are associated with increased risk of Helicobacter-induced gastric cancer (52), and IL-1 increases tumor invasiveness and metastasis by increasing expression of adhesion molecules, cytokines, and proangiogenic molecules.…”