BACKGROUND: Aberrant methylation of CpG islands in promoter regions is one of the major mechanisms for silencing of tumor suppressor genes in various types of human cancers including non-Hodgkin's lymphomas (NHL). In this study, we investigated the aberrant promoter methylation status of known or suspected tumor suppressor genes in NHLs and compared the methylation profiles between B-cell and T/NK-cell NHLs. METHODS: 54 cases of B-cell NHLs and 16 cases of T/NK-cell NHLs were examined for the methylation status of eight genes using methylation specific PCR. RESULTS: CpG islands methylation was variously found in eight genes as follows; DAPK (71%), MT1G (70%), p16 (53%), CDH1 (53%), THBS1 (56%), MGMT (27.1%), COX2 (13%), and RUNX3 (11.4%). In six cases (8 %), methylation was not observed in any of these genes. Overall methylation index of B-cell NHLs (0.48) was significantly higher than that of T/NK-cell NHLs (0.32). Of eight genes tested, THBS1 and CDH1 methylations were much more prominent in diffuse large B-cell lymphomas than in T/NK-cell NHLs or other B-cell NHLs. CONCLUSION: This study suggests that aberrant CpG island methylation is a frequent event in NHLs, and diffuse large B-cell lymphomas show overlapping but distinct methylation profiles.
Humans ; Genes, Tumor Suppressor

Recently the adenomaatous polyposis coli(APC) gene, a tumor suppressor gene, was identified and the cDNA was cloned from chromosome 5q21. Allelic deletion or point mutation of tumor suppressor genes(TSGs) has been considered as an important mechanism in development of human tumor. Point mutations affecting APC gene are seen in the hereditary syndrome, adenomatous polyposis and spordic colon cancer. However, the mutation of APC gene and other TSGs have not been described in gastric cancer. In order to identify the mutation of exon 11 of APC gene for gastric cancer, we amplified DNA extracted from paraffin-embedded tissues by polymerase chain reaction(PCR) and digested the PCR products with restriction enzyme Rsa I. We examined the DNA extracted from paraffin-embedded 44 gastric cancer tissues with lymph nodes. Eighteen(41%) among 44 were informative for the study exon 11 of the APC gene, and we found loss of heterozygosity(LOH) for APC in 6/18(33.3%). These data suggest that the point mutation or the base change of APC gene commonly occurs in gastric cancer. We conclude that the mutation of APC gene is strongly connected with development of human gastric cancer.
Humans ; Genes, Tumor Suppressor ; Stomach Neoplasms

Overexpression of the nuclear phosphoprotein p53 is the most common genetic anomaly found in primary human cancer and mutation of the tumor suppressor gene p53 has been identified in breast cancer cell lines. In this study, we evaluated the prognostic significance of p53 protein expression in patients with mammary infiltrating ductal carcinoma and its correlation with histopathologic grade, lymph node status, tumor size, p53 protein expression and survival. Among 53 cases, p53 protein expression was detected in 26(49.1%) cases by immunohistochemistry. There was no correlation between p53 protein overexpression and histopathologic grade(p=0.09) or lymph node status(p=0.38) and between survival and histopathologic grade (p=0.68) or lymph node status(p=0.52). However, p53 protein expression was significantly correlated with survival(p=0.01) and patients with p53 protein-positive tumors showed poorer survival times. But Cox multivariate analysis showed the lymph node status is significant(p=0.01). The authors conclude that the presence of mutant p53 protein and lymph node status may serve a prognostic role, in a subset of mammary infiltrating ductal carcinoma cases.
Humans ; Genes, Tumor Suppressor ; Breast Neoplasms

BACKGROUND: Our aim was to undertake a comprehensive analysis of the expression of key molecular markers in a series of pancreatic ductal adenocarcinomas and to determine their association with clinicopathologic variables. METHODS: By using immunohistochemical staining, we examined the expressions of five tumor suppressor genes (p53, p21WAF1, p16, Rb, Smad4) and a growth factor receptor (c-erbB-2) in 52 surgically resected pancreatic ductal adenocarcinomas. RESULTS: Abnormal nuclear overexpression of p53 was noted in 28/52 (53.8%) cases. Total loss of p21WAF1, p16, Rb, and Smad4 was detected in 15/52 (28.8%), 33/52 (63.5%), 4/52 (7.7%), and 26/52 (50%) cases, respectively. Overexpression of c-erbB-2 was noted in 21/52 (40.4%) cases. Forty-nine (94.2%) cases revealed aberration of at least one of the markers examined. There was a positive correlation between p53 and c-erbB-2 overexpression (p<0.05). Among the examined genes, overexpression of c-erbB-2 was found to have a positive relationship with the tumor stage (p<0.05). There was also a significant correlation between the histologic grade and the number of abnormally expressed genes per tumor (p<0.05). CONCLUSION: Among the various tumor-associated proteins evaluated in this study, c-erbB-2 could have the most likely clinical implication.
Adenocarcinoma* ; Genes, Tumor Suppressor ; Immunohistochemistry ; Pancreatic Ducts*

No abstract available.
Carcinoma, Renal Cell* ; Genes, Tumor Suppressor*

Mutation of p53 tumor suppressor gene is now recognized as the most frequent genetic alteration in human neoplasms. Although meningiomas are common intracranial tumors, little is known about the clinical significance of p53 abnormalities in meningiomas. We studied 31 cases of meningioma to investigate the significance of p53 protein expression in meningiomas and its relationships with histological and clinical parameters and proliferative activity. Classical and atypical meningiomas were 16 (51.6%) and 15 cases (43.4%), respectively. p53 protein expression was detected in 4 (25.0%) of 16 classical, and 12 (80.0%) of 15 atypical meningiomas. p53 protein expression was correlated with Ki-67 staining index, atypical type, high histologic score, sheet pattern of the neoplastic cells, vascular proliferation, and male patient (p<0.05). In conclusion, immunohistochemical evaluation of p53 protein and histologic score of meningiomas are useful in assessing the prognosis.
Genes, Tumor Suppressor ; Humans ; Male ; Meningioma* ; Prognosis

PURPOSE: Recently, it is suggested that the inhibitian of apoptosis is associated with tumorigenesis of colon. Bcl-2 gene is an important inhibitory regulator of apoptosis, and bcl-2 acts antagonistly with the wild type p53 gene, one of the tumor suppressor genes, in apoptosis. To detnmine the role of bcl-2 and p53 gene in colonic tumorigenesis, we performed the study. MATERIALS AND METHODS: We tested the tissue obtained by polypectomy and surgical resection by immunohistochemical staining for Bcl-2 and p53. RESULTS: We found that in normal colonic tissue, the Bcl-2 was sparcely expressed, and the p53 was expressed sporadically. The rate of positivity of staining was below 5%. However, in colonic adenoma and colon cancer tissue, Bcl-2 and p53 were expressed more than in nonnal colonic tissue(p<0.05). (Scoring in Colonic adenoma: Bcl-2 6.2+/-1.1, p53 5.7+/-1.0; Scoring in Colonic carcinoma: Bcl-2 4.7+/-1.0, p53 8.3+/-0.9) CONCLUSION: Our results suggested that the bcl-2 and p53 play an important role in colonic tumorigenesis.
Adenoma* ; Apoptosis ; Carcinogenesis ; Colon* ; Colonic Neoplasms ; Genes, bcl-2 ; Genes, p53* ; Genes, Tumor Suppressor

Ependymomas constitute no more than 5 to 7% of all primary CNS neoplasm and their biologic behavior is difficult to predict by microscopic appearances. Recently, many studies have attempted to correlate biologic behavior with tumor proliferation index, tumor suppressor gene and oncogene using immunohistochemical stains. We evaluated 25 cases of surgically resected intracranial ependymomas for the proliferation activity using Ki-67, and expression of p53 and bcl-2 protein with regard to the prognosis. The cases were divided into 17 ependymomas (WHO Grade II), 3 papillary ependymomas (WHO Grade II), and 5 anaplastic ependymomas. Clinically, the patients were divided into two groups, recurrent (18 cases) or non-recurrent (7 cases). The Ki-67 proliferation index was significantly higher in the recurrent group (p<0.05) and in the younger ages (correlation index=0.534). Although Ki-67 proliferation index was higher in anaplastic ependymoma, it was not significant statistically (p>0.05). p53 protein expression tended to increase in the patients who had anaplastic ependymoma and in the recurrent group. bcl-2 expression was not correlated with histologic grade or recurrence of the tumor. We conclude that Ki-67 proliferation index and p53 expression are important markers for predicting biologic behavior of ependymoma.
Coloring Agents ; Ependymoma* ; Genes, Tumor Suppressor ; Humans ; Oncogenes ; Prognosis ; Recurrence

BACKGROUND: It has been reported that the expression of protein which influences on the cell cycle is significantly involved in the development, progress, treatment response, and survival of cancer, and also that the degree of expression of p27 and CDK4 is related to the prognosis. Recent research has revealed that uteroglobin, tumor suppressor gene, is related to cell cycle. This study is focused on the relations between expression of proteins related to cell cycle and clinical index of and survival of NSCLC. METHODS: We examined immunohistochemically specimens of 110 surgically resected NSCLCs for expression of p27, CDK, Uteroglobin. Tissue array slide were obtained from 110 surgically resected NSCLCs. Immunohistochemical staining was performed by immuno-peroxidase technique using avidin-biotinylated horseradish peroxidase complex. RESULTS: In 110 patients with resected NSCLCs, the ratio of male to female was 87:13, the median age was 56.43+/-9.41 yrs. The positive staining of p27 was detected in 75% of the cases. A non-statistically significant trend toward increased p27 expression was observed in smoker and squamous cell cancer. The positive staining of CDK4 was detected in 89%, which was the highest expression of protein among 3 types. The survival ratio of CDK4 negative staining group was higher than that of positive staining group, which was significant difference(P<0.05). There was no association between p27 or uteroglobin expression and survival. CONCLUSIONS: The expression degree of CDK4 is related to the prognosis. This findings suggests that the measurement of CDK4 may be useful in identifying patient at high risk for disease recurrence and survival.
Female ; Male ; Humans ; Genes, Tumor Suppressor ; Lung Neoplasms

BACKGROUND: Abnormalities of genomic methylation patterns have been shown to play a role in the development of carcinoma, and the silencing of tumor suppressor genes is related to local de novo methylation. METHODS: Using methylation specific arbitrarily primed-Polymerase Chain Reaction (Ms AP-PCR), we identified a 322 bp sequence that contained a 5' un-translated and exon1 regions of the TPEF gene. To evaluate the inactivation of the TPEF gene through hypermethylation in hepatocellular carcinoma (HCC), we investigated the correlation between methylation patterns and TPEF expression in tumor tissues of human HCC and cell lines via a Combined Bisulfite Restriction Assay (CoBRA) and RT-PCR. RESULTS: A dense methylation pattern of the TPEF was detected in most cell lines, as well as in 10 of the 14 (71.4%) HCC tissues. In addition, loss of heterozygosity (LOH) from the TPEF gene was observed in 5 of the 14 (36%) HCC tissues. Furthermore, RT-PCR analysis revealed TPEF expression in 5 of 8 (62.5%) cell lines. Finally, treatment with a demethylating agent, 5-Aza- 2'-deoxycitidine (5-AzaC), increased the expression of TPEF mRNA. CONCLUSION: These results indicate that inactivation of the TPEF gene through hypermethylation may be a mechanism by which tumorigenesis occurs in HCC.
Humans ; Carcinoma, Hepatocellular ; Cell Transformation, Neoplastic ; Genes, Tumor Suppressor