Nuclear β-catenin expression is closely related to ulcerative growth of colorectal carcinoma

Abstract

Although most colorectal cancer develops based on the adenoma–adenocarcinoma sequence, morphologically, colorectal cancer is not a homogeneous disease entity. Generally, there are two distinct morphological types: polypoid and ulcerative colorectal tumours. Previous studies have demonstrated that K-ras codon 12 mutations are preferentially associated with polypoid growth of colorectal cancer; however, little is known about the molecular mechanism that determines ulcerative growth of colorectal cancer. β-catenin complex plays a critical role both in tumorigenesis and morphogenesis. We examined the differential expression of β-catenin and its related factors among different types of colorectal cancer in order to determine any relationship with gross tumour morphology. Immunohistochemical staining of β-catenin, E-cadherin and MMP-7 was performed on 51 tumours, including 26 polypoid tumours and 25 ulcerative tumours. Protein truncation tests and single-strand conformational polymorphism for mutation of the adenomatous polyposis coli tumour suppressor gene, as well as single-strand conformational polymorphism for the mutation of β-catenin exon 3 were also done. Nuclear expression of β-catenin was observed in 18 out of 25 (72%) cases of ulcerative colorectal cancer and seven out of 26 (26.9%) cases of polypoid colorectal cancer. A significant relationship of nuclear β-catenin expression with ulcerative colorectal cancer was found (P<0.001). However, this finding was independent of adenomatous polyposis coli tumour suppressor gene mutation and E-cadherin expression. Together with previous data, we propose that different combinations of genetic alterations may underlie different morphological types of colorectal cancer. These findings should be taken into consideration whenever developing a new genetic diagnosis or therapy for colorectal cancer.British Journal of Cancer (2002) 86, 1124–1129. DOI: 10.1038/sj/bjc/6600214 www.bjcancer.com© 2002 Cancer Research UK

Expression of β-Catenin and E-Cadherin, their Clinical Significance and Association with Complexity Index of Colon Carcinoma

“…Similarly Wang et al, showed that nuclear β-catenin expression is a good prognostic marker in CRC development [11]. In accordance with our results, some other studies demonstrate the similar findings [36][37][38]. Upregulation of β-catenin has been found associated with exaggerated activity of Wnt signaling pathway [39].…”

β-Catenin Activation Is Associated with Specific Clinical and Pathologic Characteristics and a Poor Outcome in Adrenocortical Carcinoma

“…Several observations support the importance of the activation of the Wnt/b-catenin signaling pathway in adrenal cortex tumorigenesis (11)(12)(13), as previously shown in a variety of human cancers (14)(15)(16)(17). In animal models, a constitutive activation of the Wnt/b-catenin pathway in the adrenal cortex of transgenic mice leads to the development of adrenocortical tumors with malignant characteristics (18).…”

“…The Wnt/b-catenin signaling pathway has been identified as one of the key signaling pathways in cancers (14)(15)(16)(17), having an essential pathogenic role in regulating cell growth, motility, and differentiation (29). Increasing clinical and scientific evidence supports the importance of the activation of this pathway in adrenal cortex tumorigenesis (11)(12)(13), as previously shown in a variety of human cancers (14)(15)(16)(17).…”

“…Increasing clinical and scientific evidence supports the importance of the activation of this pathway in adrenal cortex tumorigenesis (11)(12)(13), as previously shown in a variety of human cancers (14)(15)(16)(17). In this study, we used b-catenin immunohistochemistry and CTNNB1/APC mutations analysis to assess the activation of the Wnt/b-catenin signaling pathway and to investigate its prognostic value in a series of 79 patients with primary resected ACC.…”

β‐Catenin mutations in a mouse model of inflammation‐related colon carcinogenesis induced by 1,2‐dimethylhydrazine and dextran sodium sulfate

“…Although the mutations of the APC and β-catenin are rare in UC-related CRC, as compared with sporadic CRC, nuclear β-catenin expression is related to UCrelated CRC development. (39) Since the data on β-catenin mutation in UC-related CRC are limited, more studies are required to determine the role of the β-catenin mutation in UCrelated CRC. Also, expression of c-myc, cyclinD1 and c-jun, which are targets of the β-catenin/APC pathway, (17,40,41) may also influence colon carcinogenesis in the present model.…”