Different patterns of beta-catenin expression in gastric carcinomas: relationship with clinicopathological parameters and prognostic outcome (original) (raw)
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Histopathology, 2002
Different patterns of b-catenin expression in gastric carcinomas: relationship with clinicopathological parameters and prognostic outcome Aims: The cadherin±catenin complex is known to play a critical role in maintenance of cell adhesion. Additionally b-catenin (b-ct) can also take part in signal transduction and nuclear b-ct expression could be correlated with poor prognosis in several malignancies. Since, in gastric cancer, this role of b-ct is still uncertain, we investigated the expression pattern of b-ct as well as the possible prognostic role. Methods and results: b-catenin expression was immunohistochemically investigated in a retrospective series of 401 R0-resected gastric carcinomas. Out of these cases, 54 tumours (13.5%) revealed a preserved membranous b-ct expression similar to that in normal gastric mucosa. In 80 tumours b-ct expression was moderately reduced and in 117 tumours highly reduced. In 150 tumours (37.4%), no or only a weak membranous b-ct expression was found. Additionally, in 53 tumours, a strong b-ct expression could be observed in the cytoplasm with a simultaneous nuclear b-ct immunoreactivity in 17 of these 53 tumours, while nine tumours only showed nuclear immunore-activity without cytoplasmic staining. There were no signi®cant correlations between the degree of membranous b-ct expression or the different staining pattern (membranous vs. cytoplasmic/nuclear) and the grade of tumour differentiation, the histological tumour type according to Lauren, as well as with the prognostic parameters pT, pN category and vascular invasion. No associations could be found with tumour cell proliferation and the expression of E-cadherin, irrespectively of the different b-ct staining pattern. Univariate analysis revealed no in¯uence on survival, either for membranous or for cytoplasmic/nuclear b-ct expression. Conclusion: Our data on 401 tumours suggest that activation of the Wnt/b-catenin signalling does also occur in a subset of gastric carcinomas. However, in gastric cancer, neither the presence of cytoplasmic/ nuclear b-ct expression nor the reduction or loss of membranous b-ct expression is correlated with a speci®c histological tumour type, tumour progression or prognosis.
Membranous staining of β-catenin and E-cadherin expression in patients with gastric cancer
International journal of clinical and experimental pathology, 2017
BACKGROUND β-catenin and E-cadherin are adhesion molecules that promote metastatic potential through epithelial-mesenchymal transition (EMT). Although they have not been extensively studied in gastric cancers, they represent potential testable prognostic markers. METHODS We explored the association between the immunohistochemical expression of these markers and clinicopathologic parameters by retrospectively reviewing 205 cases of gastric cancer from tissue microarrays (TMA). A method was developed to evaluate for membranous staining of β-catenin and E-cadherin using grading criteria that characterized both the intensity of staining and the percentage of cells with loss of staining. RESULTS Weak membranous expression of E-cadherin and β-catenin were associated with worse overall survival (p<0.05). Abnormal expression of E-cadherin and β-catenin were significantly associated with each other (p<0.01). Loss of and/or weak membranous staining for both E-cadherin and β-catenin was ...
The Journal of Pathology, 2000
E-cadherin and its associated cytoplasmic proteins, a-, b-, and c-catenins, play an essential role in the control of epithelial differentiation. We have previously shown that loss or down-regulation of E-cadherin/catenin correlates with poor survival in advanced gastric adenocarcinoma. The aim of this study was to assess the expression of E-cadherin and catenins in early gastric cancers (EGCs). Immunohistochemical staining for E-cadherin and a-, b-, and c-catenins was performed on 41 paraf®n-embedded gastrectomy specimens of EGC using an indirect immunoperoxidase technique. The pattern of expression and cellular localization of the E-cadherin/catenin complex in tumour cells were correlated with the macroscopic appearance of the tumour according to the Japanese Endoscopic Society classi®cation. The tumours were classi®ed as follows: three type I (protruding) and 38 type II (super®cial), of which ten were type IIa (elevated), one was type IIb (¯at), and 27 were type IIc (depressed). E-cadherin and a-, b-, and c-catenins were expressed at the cell±cell junctions in normal mucosa. Forty out of 41 tumours showed abnormal expression (loss of membranous immunoreactivity and/or nuclear staining) of at least one component of the E-cadherin catenin complex. Loss of E-cadherin immunoreactivity was more frequently seen in type IIb (1/1, 100%) and type IIc (27/27, 100%) than in type I (1/3, 33%) and type IIa (1/10, 10%) ( p<0.01). Abnormal expression of E-cadherin and a-catenin was more frequently seen in diffuse-type than in intestinal type tumours ( p<0.05). Abnormal immunoreactivity of b-and ccatenin, including nuclear localization, was observed in 34% and 7.3% of tumours, respectively, but there was no signi®cant correlation with tumour type or endoscopic appearance. In conclusion, abnormal expression of the E-cadherin/catenin complex occurs in EGC and seems to correlate with macroscopic appearances.
Beta-Catenin Expression in Intramucosal Neoplastic Lesions of the Stomach
Oncology, 2003
Objective: To clarify roles of beta-catenin in the early stage of gastric tumorigenesis, we investigate beta-catenin expression in stomach intramucosal neoplasms. Methods: For immunohistochemistry, 84 gland-forming neoplasms and 17 signet-ring cell carcinomas were examined. The gland-forming neoplasms were grouped according to the Vienna classification: group A (lowgrade adenoma/dysplasia), group B (high-grade adenoma/dysplasia) and group C (intramucosal carcinoma). Results: Strong nuclear expression was detected not only in group C (21.4%) but in groups A (20.8%) and B (11.2%). Strong cytoplasmic expression was detected in groups A, B and C: 16.7, 11.2 and 16.7%, respectively. Loss of membranous stainings (LOM) were also detected in groups A, B and C: 20.8, 22.2 and 31.0%, respectively. No significant difference was found among groups A, B and C with respect to nuclear, cytoplasmic, and membranous expression. Regarding signet-ring cell carcinomas, all cases were essentially negative for nuclear expression and 11.8% of the cases showed weak cytoplasmic expression as well as LOM. There were obvious differences between gland-forming adenocarcinoma and signet-ring cell carcinoma with respect to nuclear and cytoplasmic expression but not in terms of membranous expression. Conclusion: These findings suggest that beta-catenin expression does not always reflect the malignant transformations in the early stage of gastric tumorigenesis.
…, 2010
Aims: b-Catenin is an important molecule in cancer biology. Membranous b-catenin enhances cellular differentiation and inhibits invasion by its action on E-cadherin. The aim was to ascertain whether the cellular expression of these molecules in colorectal and oesophageal cancer specimens is associated with survival in patients with gastrointestinal cancer. Methods and results: Tumour samples from 149 patients undergoing resection for colorectal adenocarcinoma and 147 patients undergoing resection for oesophageal adenocarcinoma were retrospectively analysed using immunohistochemical techniques to assess b-catenin expression. Increasing b-catenin expression in the cytoplasm was associated with improved survival for colorectal cancer cases on both univariate (P = 0.003) and multivariate (P = 0.01) analysis. In addition, increased expression in the most recent cohort of oesophageal adenocarcinoma patients was associated with improved TNM staging (P = 0.007). Membrane expression was weakly associated with survival in colorectal cancer on univariate analysis (P = 0.09), but not on multivariate analysis (P = 0.21). Complete absence of b-catenin expression at all three sites was associated with reduced 5-year survival in colorectal cancer. Conclusions: This is one of the largest prognostic studies of b-catenin in gastrointestinal adenocarcinoma. It shows that low levels of cytoplasmic b-catenin expression are associated with reduced survival in patients with colorectal cancer as well as worse TNM staging in oesophageal adenocarcinoma (a recognized surrogate end-point for survival). We believe this is the first time that this has been reported. This finding should be tested prospectively in oncological trials to validate whether the presence of cytoplasmic b-catenin could be used as a prognostic marker for less aggressive disease.
Gastroenterology, 2000
Background and aims-The role of altered cell adhesion is critical for the development of epithelial cancers. E-cadherin plays an important role in the maintenance of cell-cell adhesion and its function is thought to be regulated by its associated cytoplasmic proteins, such as-catenin and-catenin. To determine the role of-catenin expression in gastric carcinogenesis, we studied its expression in human gastric cancer and in the gastric mucosa of first degree relatives with no clinical disease. Methods-Catenin expression was assessed by immunohistochemical analysis and reverse transcriptase-polymerase chain reaction (RT-PCR) using gastric tissue specimens from patients with gastric cancer and from the gastric mucosa of first degree relatives of gastric cancer patients and healthy controls. Results-mRNA levels of-catenin were reduced or absent in 13 of 19 gastric cancer tissues, which diVered significantly from levels found in the tumour free gastric mucosa of cancer patients (p<0.05). Of the cancer samples with altered-catenin mRNA levels,-catenin expression was negative in seven and decreased in six cases. Interestingly, decreased-catenin mRNA expression also occurred in the mucosa of the corpus (11/ 18) and antrum (4/18) of first degree relatives. In the corpus biopsies-catenin expression was more often decreased or lost compared with the antrum biopsies in first degree relatives and healthy controls (p<0.05). Immunohistochemical analysis revealed membranous expression of-catenin in gastric cancer cells and the non-malignant gastric epithelium. However, some cancers also exhibited loss of membranous staining. Generally, loss or downregulation of-catenin mRNA in the gastric mucosa was associated with Helicobacter pylori infection (p<0.05). Conclusion-Our findings suggest that loss or downregulation of-catenin expression may be an early event in gastric carcinogenesis and may be associated with H pylori infection.
Alterations of E-cadherin and β-catenin in gastric cancer
1, 16, 2001
BACKGROUND: The E-cadherin-catenin complex plays a crucial role in epithelial cell-cell adhesion and in the maintenance of tissue architecture. Perturbation in the expression or function of this complex results in loss of intercellular adhesion, with possible consequent cell transformation and tumour progression. METHODS: We studied the alterations of E-cadherin and beta-catenin in a set of 50 primary gastric tumours by using loss of heterozygosity (LOH) analysis, gene mutation screening, detection of aberrant transcripts and immunohistochemistry (IHC). RESULTS: A high frequency (75%) of LOH was detected at 16q22.1 containing E-cadherin locus. Three cases (6%) showed the identical missense mutation, A592T. This mutation is not likely to contribute strongly to the carcinogenesis of gastric cancer, because a low frequency (1.6%) of this mutation was also found in 187 normal individuals. We also detected a low frequency (0.36%, 0%) of this mutation in 280 breast tumours and 444 other tumours, including colon and rectum, lung, endometrium, ovary, testis, kidney, thyroid carcinomas and sarcomas, respectively. We also analyzed the aberrant E-cadherin mRNAs in the gastric tumours and found that 7 tumours (18%) had aberrant mRNAs in addition to the normal mRNA. These aberrant mRNAs may produce abnormal E-cadherin molecules, resulting in weak cell-cell adhesion and invasive behaviour of carcinoma cells. Reduced expression of E-cadherin and beta-catenin was identified at the frequency of 42% and 28%, respectively. Specially, 11 tumours (22%) exhibited positive cytoplasmic staining for beta-catenin IHC. An association was found between reduced expression of E-cadherin and beta-catenin. Moreover, an association was detected between reduced expression of E-cadherin and diffuse histotype. CONCLUSION: Our results support the hypothesis that alterations of E-cadherin and beta-catenin play a role in the initiation and progression of gastric cancer.
Arquivos brasileiros de cirurgia digestiva : ABCD = Brazilian archives of digestive surgery
Gastric cancer is the fifth most frequent cancer and the third most common cause of cancer-related deaths worldwide.It has been reported that Wnt/ betacatenin pathway is activated in 30-50% of these tumors. However,the deregulation of this pathway has not been fully elucidated. To determine the expression of E-cadherin, betacatenin, APC, TCF-4 and survivin proteins in gastric adenocarcinoma tissues and correlate with clinical and pathological parameters. Seventy-one patients with gastric adenocarcinoma undergoing gastrectomy were enrolled. The expression of E-cadherin, betacatenin, APC, TCF-4 and survivin proteins was detected by immunohistochemistryand related to the clinical and pathological parameters. The expression rates of E-cadherin in the membrane was 3%; betacatenin in the cytoplasm and nucleus were 23,4% and 3,1% respectively; APC in the cytoplasm was 94,6%; TCF-4 in the nucleus was 19,4%; and survivin in the nucleus 93,9%. The expression rate of E-cadherin was correlated ...
Romanian journal of …, 2010
Gastric cancer is one of the most aggressive malignancies, as incidence and as evolution as well. Although, due to the new findings about etiology, carcinogenesis, precancerous conditions and their detection, as well as the treatment, in the latest decade, there is an improvement in these data, gastric cancer remains a redoubtable enemy because of its incidence, prevalence and mortality. Researches are focusing on early detection of precursor lesions and on establishing their reversibility potential by bringing more clinical and statistical information and by setting new clinical hypotheses. In this context, the present article is trying to study immunohistochemical expression of two oncogenic markers, the cell adhesion protein antibodies E-cadherin and β-catenin. Cell to cell and cell to extracellular matrix interactions are crucial for neoplastic transformation and for metastasizing process. The importance of these antibodies in maintaining cell adhesion suggests that their abnormal expression is playing an important role in tumorigenesis.
Romanian journal of internal medicine = Revue roumaine de médecine interne, 2010
Gastric cancer is one of the most aggressive malignancies, as incidence and as evolution as well. Although, due to the new findings about etiology, carcinogenesis, precancerous conditions and their detection, as well as the treatment, in the latest decade, there is an improvement in these data, gastric cancer remains a redoubtable enemy because of its incidence, prevalence and mortality. Researches are focusing on early detection of precursor lesions and on establishing their reversibility potential by bringing more clinical and statistical information and by setting new clinical hypotheses. In this context, the present article is trying to study immunohistochemical expression of two oncogenic markers, the cell adhesion protein antibodies E-cadherin and beta-catenin. Cell to cell and cell to extracellular matrix interactions are crucial for neoplastic transformation and for metastasizing process. The importance of these antibodies in maintaining cell adhesion suggests that their abn...