Relationship between β -catenin expression and prognostic parameters of colorectal carcinomas (original) (raw)
Related papers
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...
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.
Medicine and Pharmacy Reports
Background. Cancer is one of the world’s biggest health care challenges, with colorectal cancer (CRC) being one of the three most frequently encountered malignancy worldwide. The main cause of mortality associated with CRC is tumour invasion and metastasis. Pathogenesis of CRC is a multistep process, during which different molecular pathways come into play. The cardinal genomic alteration that has been found universally present in CRC is a mutation in the adenomatous polyposis coli gene (APC). APC mutation causes unrestricted action of the Wnt signaling pathway which subsequently enhances the intracellular accumulation of a protein called beta-catenin, responsible for cell proliferation, differentiation and enhanced survival of colorectal epithelial cells. Aim. This study was conducted to analyze beta–catenin expression in various colorectal neoplasms, and its change with respect to different grades and stage of colorectal adenocarcinoma. Study design. This was a cross-sectional obs...
Nuclear β-catenin expression as a prognostic factor in advanced colorectal carcinoma
World Journal of Gastroenterology, 2008
To investigate the changing pattern of β-catenin expression and its prognostic value in advanced colorectal cancer (CRC). METHODS: Archival tumor samples were analyzed for β-catenin using immunohistochemistry (IHC) in 95 patients with advanced CRC. RESULTS: Membranous β-catenin expression was found in the normal colorectal epithelium. Almost 1 0 0 % o f C R C c a s e s s h o w e d m e m b ra n o u s a n d cytoplasmic expression, and 55 (58%) cases showed nuclear expression. In univariate (Kaplan-Meier) survival analysis, only the nuclear index (NI) was a significant predictor of disease-free survival (DFS) (P = 0.023; n = 35), with a NI above the median associated with longer DFS (34.2 mo) than those with a NI below the median (15.5 mo) (P = 0.045, ANOVA). The other indices were not significant predictors of DFS, and none of the three tested indices (for membranous, cytoplasmic, or nuclear expression) predicted diseasespecific survival (DSS). However, when dichotomized as positive or negative nuclear expression, the former was a significant predictor of more favorable DFS (P = 0.041) and DSS (P = 0.046). CONCLUSION: Nuclear β-catenin expression provides additional information in predicting patient outcome in advanced CRC.
?-Catenin Expression in Primary and Metastatic Colorectal Carcinoma
International Journal of Cancer, 1999
-catenin plays a fundamental role in the regulation of the E-cadherin-catenin cell adhesion complex. It also functions in growth signalling events, independently of the cadherincatenin complex, and these signalling pathways are disturbed in colorectal cancer. Mutations in either the APC or -catenin genes in colorectal cancer cells result in up-regulation of protein expression and subsequent cytoplasmic and nuclear distribution of -catenin. In this study, we examined -catenin expression in 47 primary colorectal tumors and the corresponding liver metastases. Immunohistochemical studies demonstrated loss of membranous -catenin expression in 26% of primary tumors and 60% of liver metastases and a concomitant increase in cytoplasmic and nuclear staining. Widespread nuclear expression of -catenin was found in 64% of primary tumors and 21% of liver metastases. No associations were found between any form of -catenin expression and either tumor stage or tumor grade. Cellular distribution of -catenin was also examined by detergent extraction and Western blot analysis in 16 primary tumors and 23 liver metastases. This analysis showed that most tumors demonstrated reduced -catenin in the cytoskeletal fraction and increased -catenin in the cytosolic fraction. Furthermore, 3 liver metastases were found to contain a truncated -catenin protein of approximately M r 80,000. Immunoprecipitation studies showed that the truncated -catenin proteins only bound weakly to E-cadherin and -catenin compared with non-truncated -catenin. These results demonstrate gross alterations in the cellular distribution of -catenin in primary colorectal cancers with metastatic potential, as well as in the metastatic tumors. These changes may be the consequence of APC or -catenin gene mutations, or possibly result from a post-translational modification of the E-cadherin-catenin complex. Int.
World Journal of Gastroenterology, 2008
To examine the expression of beta-catenin in colorectal cancer and look for association with other clinico-pathological parameters. METHODS: Tumor samples from 163 cases of colorectal cancer (CRC) who had undergone primary colectomy between May, 1998 and November, 2002 with complete follow-up data for either 5 years or until death were recruited for a beta-catenin immunohistochemical study. The percentage of immunoreacted tumor cells was defined as overall staining density (OSD) and percentage of cells having nuclear localization was counted as nuclear staining density (NSD). Univariate exploration used log-rank test and multivariate survival analysis used Cox's hazard regression model. RESULTS: B eta-catenin immunoreactivity was detected in 161 samples (98.8%), of which 131 cases had nuclear staining. High OSD (≥ 75%), detected in 123 cases (75.5%), was significantly associated with earlier clinical staging (P < 0.01), lower nodal status (P = 0.02), non-metastatic status (P < 0.01) and better differentiation (P = 0.02). Multivariate analysis found that high OSD was independently associated with better survival [Cox's hazard ratio 0.51, 95% confidence interval (CI) 0.31-0.83]. Although high NSD (≥ 75%) was correlated with high pre-operative serum CEA (P = 0.03), well differentiation (P < 0.01), and increased staining intensity (P < 0.01), the parameter was not significantly associated with survival. CONCLUSION: Unlike previous reports, the study did not find a predictive value of nuclear beta-catenin in CRC. Instead, the overall expression of beta-catenin in CRC showed an association with better differentiation and earlier staging. Moreover, the parameter also independently predicted superior survival.
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.
Prognostic Significance of Nuclear β-Catenin Expression in Patients with Colorectal Cancer from Iran
Iranian Red Crescent Medical Journal, 2015
Background: Beta catenin plays a key role in cancer tumorigenesis. However, its prognostic significance in patients with colorectal cancer (CRC) remains controversial. It has been demonstrated that 90% of all tumors have a mutation in individual components of multiple oncogenes in Wnt/β-catenin pathway. Accumulation of nuclear β-catenin in cytoplasm leads to uncontrolled cell proliferation. Thus, nuclear β-catenin accumulation may be a valuable biomarker associated with invasion, metastasis and poor prognosis of CRC. Objectives: In this study the prognostic value of beta catenin expression in 165 Iranian CRC patients was evaluated. Patients and Methods: In this cross sectional retrospective study immunohistochemistry analyses of formalin-fixed paraffin-embedded (FFPE) tumor tissues were performed to characterize the expression of nuclear β-catenin in a series of 165 Iranian patients with colorectal carcinoma. Heat-induced antigen retrieval using the microwave method was applied for all staining procedures. Staining was scored independently by two observers, and a high level of concordance (90%) was achieved. Statistical analysis was done using the SPSS software for Windows, version 13.0.0 (SPSS Inc., Chicago, IL). Two-tailed P < 0.05 was considered statistically significant. Results: The patients consisted of 85 males and 80 females. Eighty-eight patients had primary tumor of the rectum and sigmoid, while 77 patients had primary tumor of the colon. The mean period of follow-up was 47.2 ± 10 months and the median period of follow-up was 38 months (range 6-58) for each patient. Of 165 tumors, 32 tumors (19.39 %) showed expression of β-catenin and 133 (80.6 %) were negative for β-catenin expression. Based on our findings the distribution of Microsatellite Instability (MSI) status differed between patients with nuclear β-catenin positive and negative tumors and this difference was significant (P = 0.001). Patients with nuclear β-catenin positive expression profile were found to be younger than patients with negative nuclear β-catenin expression (P = 0.010). Univariate and multivariate analysis showed that tumors with β-catenin expression had a poorer prognosis compared to tumors without β-catenin expression. Conclusions: According to our findings, the distribution of nuclear b-catenin expression is a poor prognostic marker in patients with colon cancer.
Cadherin-catenin expression in primary colorectal cancer: a survival analysis
British journal of cancer, 1999
Both cell adhesion and cell signalling events are mediated by components of the cadherin-catenin complex. Loss of expression of the components of this complex have been shown to correlate with invasive behaviour in many tumour types although their exact role in colorectal cancer remains unclear. Immunohistochemical analysis of the expression of components of the cadherin-catenin complex in colorectal cancers from 60 patients was undertaken. Loss of memberanous expression of E-cadherin, alpha-catenin and beta-catenin was demonstrated in 52%, 85% and 40% of tumours respectively. Focal nuclear expression of beta-catenin (< 75% of cells per section), usually associated with cytoplasmic expression, was clearly demonstrated in 19 (32%) tumours while widespread nuclear expression (> 75% of tumour cells per section) was seen in 11 (18%) tumours. Loss of membranous alpha-catenin expression significantly correlated with tumour de-differentiation (P = 0.009). There was a trend towards an...
Prognostic and Diagnostic Significance of β-Catenin Nuclear Immunostaining in Colorectal Cancer
Clinical Cancer Research, 2004
In the present study, we investigated the prognostic and diagnostic significance of β-catenin nuclear immunostaining in 60 specimens of normal colorectal tissue; 180 specimens of colorectal polyps, adenomas, and carcinomas; and 40 specimens from patients with the simultaneous occurrence of polyps, adenomas, and carcinomas. Additional specimens from 59 patients with colorectal carcinoma and 14 patients with adenoma who subsequently developed carcinoma were examined for possible survival study. Immunohistochemical staining showed that the occurrence of nuclear β-catenin correlated with the sequential stages in colorectal carcinogenesis, in which positive staining was observed in 0% of normal tissues, 8% of polyps, 92% of adenomas, and 100% of carcinomas. High immunohistochemical scores in colorectal carcinoma were significantly associated with lymph node metastasis and poor survival. Adenomas associated with synchronous or metachronous carcinomas showed significantly higher levels of ...