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

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

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

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

No abstract available.
Cell Line* ; Genes, Tumor Suppressor* ; Humans* ; Lung Neoplasms* ; Lung*

BACKGROUND: Parafibromin is a recently defined tumor suppressor gene. The aim of our study was to determine the relationships of parafibromin expression in urothelial carcinomas (UCs) with prognostic parameters and to evaluate the use of parafibromin as a potential marker of UC. METHODS: Parafibromin expression was assessed in 49 UC specimens using immunohistochemistry. The correlations between parafibromin expression and clinical and pathologic parameters were investigated. RESULTS: Of the patients, 42 (85.7%) were male, and the mean age was 69.6 +/- 8.2 years (range, 54 to 88 years). Morphologically, the UCs were divided into two groups: papillary (n = 27) and non-papillary (n = 22). There were seven low-grade (14.3%) and 42 high-grade (85.7%) tumors. Parafibromin was negative in 13 tumors (26.5%), partially positive in 19 tumors (38.8%), and positive in 17 tumors (34.7%). Parafibromin expression was more negative in UCs from upper urinary locations (n=17) and with muscularis propria invasion (n=28), which was statistically significant (p = .009 and p = .007, respectively). There was no statistically significant relationship between parafibromin expression and gender, age, tumor grade, survival, or disease-free survival. CONCLUSIONS: We found that UC cases with parafibromin positivity had less of a tendency to show muscularis propria invasion and were more commonly located in the lower urinary system. These results need to be confirmed with studies based on larger case series.
Disease-Free Survival ; Genes, Tumor Suppressor ; Humans ; Immunohistochemistry ; Male

An immunohistochemical stain for p53 tumor suppressor gene product was performed in 59 primary lung cancers to study the relation between its expression and type of the tumor, degree of tumor differentiation,clinical stage and smoking. The results were as follows: 1. The expression of mutant p53 protein was noted in 28 of 59 cases(47.5%) of primary lung cancers. The p53 protein was expressed in 21 of 35(60%) squamous cell carcinomas, in 6 of 21(28.6%) adenocarcinomas, and 1 of 1(100%) small cell carcinoma. There was a significant difference in expression of p53 among the different histologic types of lung cancer(p<0.05). 2. The incidence of p53 protein expression did not correlate with the degree of tumor cell differentiation or the clinical stage of lung carcinoma(p>0.05). 3. The incidence of p53 protein expression was higher in smokers(current: 75%, former: 46.2%) than in non-smokers(5.6%) and was increased in direct proportion to the pack years. There was a statistically significant correlation between p53 expression and smoking(p<0.05). The mutation of p53 gene may often be an early event in the development of lung cancer and it is suggested that the smoking known as a risk factor for the development of the lung cancer may be associated with the transformation of p53 tumor suppressor gene into mutant p53 gene or oncogene.
Incidence ; Risk Factors ; Genes, Tumor Suppressor ; Lung Neoplasms