Assessment of beta-catenin expression by immunohistochemistry in colorectal neoplasms and its role as an additional prognostic marker in colorectal adenocarcinoma (original) (raw)
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Archives of Medical Research, 2015
Background and Aims. b-Catenin and adenomatous polyposis coli (APC) are major components of the Wnt pathway. This study aimed to investigate the expression of b-catenin and APC in tumors and lymph nodes in colorectal cancer (CRC) patients and the mutational spectrum of the genes coding these proteins. Methods. Expression of APC and b-catenin was examined in 124 tumors and 41 lymph nodes. Exon 3 of CTNNB1 and the mutation cluster region (MCR) in exon 15 of the APC gene were screened for mutation by PCR-sequencing. Results. Nuclear/cytoplasmic immunostaining of b-catenin was detected in 58.1 and 48.8% in tumors and lymph nodes, respectively. In tumors, abnormal expression of b-catenin correlated with tumor size and with those in lymph nodes. Membranous b-catenin expression occurred in 41.9 and 14.6% of tumors and lymph nodes, respectively. In tumors, lack of membranous b-catenin correlated with high invasiveness and metastatic potential. Positive immunostaining for APC was observed in 2 and 14% of tumors and lymph nodes, respectively. Overexpression in nucleus/cytoplasm and lack of membranous b-catenin significantly correlated with a reduced overall survival. Among 25 tumors, four harbour mutation in Ser33 and Ser47 and overexpress the b-catenin in the nucleus/cytoplasm. Mutations were identified in the APC gene in 13 tumors and six mutations were novel. Conclusions. Positive association between aberrant expression of b-catenin in the nucleus/cytoplasm of tumors and lymph nodes was observed. Nucleus/cytoplasmic accumulation of b-catenin and loss of membranous expression are related to reduced survival and could serve as a candidate prognostic predictor.
Cancer Epidemiology, Biomarkers & Prevention, 2012
Background: Malfunctioning of the adenomatous polyposis coli (APC)/β-catenin signaling pathway is both an early and common event in sporadic colorectal cancer. To assess the potential of APC/β-catenin signaling pathway markers as treatable, preneoplastic biomarkers of risk for colorectal neoplasms, we conducted a pilot colonoscopy-based case–control study (51 cases and 154 controls) of incident, sporadic colorectal adenoma. Methods: We evaluated APC, β-catenin, and E-cadherin expression in normal mucosa from the rectum and ascending and sigmoid colon using automated immunohistochemical and quantitative image analysis. Diet, lifestyle, and medical history were assessed with validated questionnaires. Results: In the normal rectal mucosa, the ratio of the proportion of APC expression in the upper 40% of crypts with total β-catenin expression (APC/β-catenin score) was 14.3% greater in controls than in cases [P = 0.02; OR, 0.40; 95% confidence interval (CI), 0.14–1.14]. Compared with con...
Journal of Evidence Based Medicine and Healthcare, 2021
BACKGROUND Colorectal carcinoma is the most frequently encountered malignancy worldwide. The main cause of mortality associated with colorectal malignancy is tumour invasion and metastasis. The major genomic alteration that has been found in colorectal carcinoma is mutation in the adenomatous polyposis gene. Mutated APC causes unrestricted action of the Wnt signalling pathway which results in accumulation of the β - catenin protein in the nucleus responsible for cell proliferation, differentiation and enhanced survival of colorectal epithelial cells. Role of β - catenin expression as a prognostic marker needs to be studied. It will help in aiding the possibility of the future of anti β - catenin targeted chemotherapy for the treatment of colorectal cancers. METHODS A total of 85 samples from histopathologically proven cases of adenocarcinoma colon were taken. Histomorphological features and their immunohistochemical expression of β - catenin were studied. Data thus obtained was anal...
The Indonesian Journal of Gastroenterology Hepatology and Digestive Endoscopy, 2010
Background: Adenomatous polyposis coli (APC) gene mutation was found in up to 80% of cases of sporadic colorectal cancers and adenomas. Loss of APC protein function has been known as one of the early process in colorectal carcinogenesis. This event leads to the accumulation of beta catenin in the cytoplasm and nucleus and subsequently activates target genes that regulate cell proliferation and apoptosis. The aim of this study was to investigate the alteration of subcellular beta catenin expression in the progression of colorectal cancer. Method: This cross-sectional study was conducted with 30 paraffin-embedded tissue sections each of normal colorectal mucosa, adenomas and carcinomas. Alteration of beta catenin expression in membranous, cytoplasmic, and nuclear compartments were evaluated by immunohistochemical staining. Results: Beta catenin immunoreactivity was detected in all cases, of which 87 (96.7%) cases showed membranous expression, 78 (86.7%) cases had cytoplasmic and 51 cases (56.7%) had nuclear expression. Such results were statistically significant (p < 0.000). All normal colorectal epithelium showed membranous beta catenin expression with 18 (60.0%) cases showed cytoplasmic and no nuclear beta catenin expression was found. Strong cytoplasmic expression was found in 17 (56.7%) adenomas and 25 (83.3%) carcinomas; while strong nuclear expression was found in 12 (40.0%) adenomas and 17 (56.7%) carcinomas. There was no statistical significant association between beta catenin expression in the membranous, cytoplasmic and nuclear compartment with the degree of dysplasia or differentiation of tumor (p > 0.05). Conclusion: Altered subcellular expression of beta catenin occurs as the oncogenic process develops from adenoma into carcinoma. Such finding reflects the importance of beta-catenin in colorectal carcinogenesis.
Relationship between β -catenin expression and prognostic parameters of colorectal carcinomas
Turkish Journal of Pathology, 2013
Objective: Colorectal carcinomas are the most frequent tumors of the gastrointestinal tract. β-catenin, which is related to cadherins, is a cytoplasmic protein responsible for intercellular adhesion. It is also an important component in the Wnt signal pathway. Recent studies have shown structural alterations in the APC gene and axin in patients with colorectal carcinoma, along with β-catenin. We aimed to compare β-catenin expression, which is a prognostic factor itself, with other prognostic parameters. Material and Method: A total of 70 patients who had surgical intervention for colorectal malignancies between January 1994 and December 2003 were included in the study. Fift y-nine of the patients (84.3%) were male, 11 of the patients (15.7%) were female; their ages varied between 24 and 82 (mean 60.3 ±15.2) years. Paraff in blocks were immunohistochemically stained for β-catenin. Th e number of stained cell nuclei was assessed according to the stage of disease using the TNM classification, histological grade, lymphatic invasion, vascular invasion and tumor's local invasion. Results: When groups constituted according to tumor histologic grade were compared for prognostic parameters in terms of stain density for β-catenin and number of stained cell nuclei, stain density was mild (+) and the number of stained nuclei was smaller in well-diff erentiated groups while stain density was strong (+++) and the number of stained nuclei was higher in poorly diff erentiated groups. Th ere was a relation between β-catenin expression and diff erentiation grade, lymph node metastasis, stage and tumor size but not with vascular invasion. Conclusion : Th ese data indicate that β-catenin, with functions in cell homeostasis and relations with the APC gene, has a substantial role in colorectal carcinogenesis.
β-Catenin expression and allelic loss at APC in sporadic colorectal carcinogenesis
Virchows Archiv, 2002
β-catenin is involved in E-cadherin-mediated cell adhesion, intracellular signal transduction, and also interacts with adenomatous polyposis coli (APC) protein. We previously found that 31% of colorectal adenomas and 84% of carcinomas showed reduced membranous staining of β-catenin, while 46% of adenomas and 79% of carcinomas displayed β-catenin nuclear expression. Importantly, a reciprocal relationship between reduced membranous and increased nuclear β-catenin expression was demonstrated in the development from adenoma to carcinoma. To clarify whether this relates to an abnormality of the APC gene (APC), we have now studied allele loss in microdissected tissues from 74 adenomas and 21 carcinomas (sporadic cases, previously immunostained for β-catenin) by analysis of the microsatellites D5S346, D5S82 and D5S299. Fifty-five tumors (57.8%) showed allele loss at APC (no difference between adenomas and carcinomas). Thirty-one of these 55 (31/55, 56.4%) displayed both increased nuclear localization and reduced membranous staining of β-catenin, and thirteen tumors (13/55, 23.6%) manifested either nuclear expression without changes in membranous expression or reduced membranous staining without nuclear expression (9 and 4 cases, respectively), while 11 (11/55, 20.0%) preserved normal membranous expression. Adenomas and carcinomas showing both nuclear and reduced membranous expression of β-catenin, compared with those with normal membranous expression, tended to show allele loss (P<0.01). In addition, 24 (24/95, 25.6%) tumors showed a change in the pattern of β-catenin expression, but did not exhibit allele loss. These results suggest that although there may be a number of mechanisms responsible for changes in β-catenin expression in colorectal tumors, dysfunction of APC may be the major cause of this phenomenon.
Medical Research Archives
Background: Colorectal carcinoma (CRC) is the most common and one of the main causes of mortality and morbidity globally among gastrointestinal tract tumors. A benign polyp is the first step in the multistage pathogenesis of colorectal cancer, which eventually progresses to an adenoma and a carcinoma. Wnt/ βeta-catenin signaling pathway plays an initiating and rate-limiting role in colorectal tumorigenesis. Aim of the work: To evaluate the association between the immunohistochemistry (expression of E-cadherin, and β-catenin with the histopathological grade, and stage of colorectal cancer. Materials and Methods: The study was retrospectively collected from the archives of the Department of Pathology in Tobruk Medical Center. Eighty-two histopathologically confirmed cases of adenomas (n = 48) (tubular, villous, and tubulovillous), and colorectal adenocarcinoma (Mucinous, and Non-mucinous) (n = 34) were included in this study over two years (2021-2023). The histopathological diagnosis,...
Pathology & Oncology Research, 2011
Wnt/β-catenin pathway plays an important role in initiation and progression of colorectal oncogenesis. The aim of this study was to determine expression and localization of E-cadherin, β-catenin and Wnt-1 proteins in colorectal tumors. Expression of β-catenin, E-cadherin and Wnt-1 was determined by immunohistochemistry on advanced colorectal cancers. Abnormal expression of Ecadherin, β-catenin, Wnt-1 was observed. Additionally, we revealed correlations between levels of studied proteins and histoclinical data. In multivariate analysis nuclear β-catenin, higher carcinoembryonic antigen serum level before treatment, female sex and tumor localized in colon or rectum were independent unfavorable prognostic factors. These findings support the hypothesis that Wnt/β-catenin pathway plays an important role in advanced colorectal carcinoma. Keywords β-catenin. E-cadherin. Wnt-1. Wnt signaling pathway. Advanced colorectal carcinoma. Prognostic factor Abbreviations APC Adenomatous polyposis coli βTrCP Ubiquitin ligase protein CTNNB1 β-catenin gene CDH1 E-cadherin gene CEA Carcinoembryonic antigen CI Confidence interval CKI Casein kinase I CRC Colorectal carcinoma DFS Disease free-survival FAP Familial adenomatous polyposis FOLFIRI 5-fluorouracil leucovorin and irinotecan FOLFOX4 5-fluorouracil leucovorin and oxaliplatin GSK3β Glycogen synthase kinase 3β K-RAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog HR
Curēus, 2024
Background Colorectal cancer (CRC) is a significant global health challenge with high mortality rates. Dysregulation of β-catenin, epithelial-mesenchymal transition (EMT), and adenomatous polyposis coli (APC) are crucial in CRC development. Mutations in the APC gene lead to aberrant β-catenin expression, a key player in CRC pathogenesis. β-catenin not only influences canonical Wnt signaling but also regulates EMT. This study investigated the correlation between APC mutations, β-catenin dysregulation, and EMT induction in CRC. Methodology Tissue samples from 96 CRC patients and 40 para-cancerous normal tissues were collected and subjected to immunohistochemistry to assess β-catenin, E-cadherin, ZEB1, Snail, and vimentin expression. Genomic DNA was extracted and analyzed for APC mutations. Next-generation sequencing was employed for data analysis. Results Aberrant β-catenin expression was found in 82.3% of CRC cases and correlated with advanced clinicopathological factors. Aberrant β-catenin expression was associated with age (p=0.01), tumor invasion depth (p=0.03), nodal/distant metastasis (p=0.001 and 0.004), and vascular invasion (p=0.001). Aberrant βcatenin was correlated with EMT status. A positive correlation was observed between aberrant β-catenin expression and ZEB1 (p=0.001), Snail (p=0.001), vimentin (p=0.001), and loss of membranous E-cadherin (p=0001). Coexistence of aberrant β-catenin and EMT markers was associated with advanced CRC progression. Cancerous tissues displayed higher aberrant β-catenin and EMT markers expression than paracancerous tissues. APC mutations were present in 59.3% of cases, with 91.2% of mutated APC cases showing aberrant β-catenin expression. The coexistence of APC mutation and aberrant β-catenin expression was correlated with the clinical outcomes of CRC patients. Mutated APC cases exhibited significantly increased EMT marker expression. Conclusion This study underscores the importance of aberrant β-catenin expression in CRC progression, linked to APC mutations and EMT induction. Understanding these relationships could aid in developing targeted therapies for CRC.
APC and beta-catenin protein expression patterns in HNPCC-related endometrial and colorectal cancers
Familial cancer, 2005
The adenomatous polyposis coli (APC) and beta-catenin (CTNNB1) genes are the two major components of the Wnt signaling pathway that has been shown to play an important role in the formation of certain cancers. The overactivation of the pathway, which results in abnormal accumulation of beta-catenin protein in nuclei, contributes to most colorectal cancers (CRCs), both sporadic and hereditary, as well as sporadic endometrial cancers (ECs). Here, we studied the involvement of APC and beta-catenin in hereditary nonpolyposis colorectal cancer (HNPCC)-related ECs, and compared the expression patterns to those in HNPCC-related CRCs. Nineteen ECs and 31 CRCs derived from HNPCC patients were immunohistochemically stained with anti-APC- and anti-beta-catenin-antibodies. Tumor-specific loss of APC was observed in 16 of endometrial cancers (3 of 19) and in 39 of colorectal cancers (12 of 31). Consistently, the loss of APC expression was associated with nuclear beta-catenin staining. Altogether...