Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Frequent recurrences and multicentricity of bladder cancer suggest that alterations of the urothelium distant from the tumor may be relevant to prognosis. In this study immunohistochemistry and fluorescence in situ hybridization (FISH) were used to examine expression of p53, erbB-2, and epidermal growth factor receptor (EGF-r), genomic aberrations, and tumor cell proliferation (Ki67 LI) in normal and dysplastic urothelium. Biopsy specimens examined included normal urothelium (n = 40), mild dysplasia (n = 34), moderate dysplasia (n = 18) and carcinoma in situ (CIS; n = 20). Several different oncogene expression patterns were found, only some of which were associated with dysplasia. EGF-r expression was equally frequent in normal and dysplastic urothelium and showed a strong association with Ki67 LI (P < .0001). A purely superficial erbB-2 positivity was present in both normal and dysplastic biopsies. However, diffuse erbB-2 positivity and p53 overexpression were both associated with advanced dysplasia (P < .0001 each). FISH analysis showed erbB-2 gene amplification and p53 deletions in selected CIS, as well as a marked chromosome 17 copy number heterogeneity in all six CIS examined. These findings indicate a considerable genomic instability in bladder CIS. They show that both erbB-2 and p53 are altered during malignant transformation. Detectable oncogene expression alone, however, is not diagnostic of malignancy in bladder urothelium.
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PMID:Patterns of p53, erbB-2, and EGF-r expression in premalignant lesions of the urinary bladder. 767 97

Since human trophoblast undergoes extensive proliferation and exhibits invasive growth comparable to that of a malignant tumour, human placenta at various different stages of gestation was investigated immunohistochemically with the monoclonal antibody Ab-6 for expression of the p53 tumour suppressor gene. p53 protein was detected in the nuclei of a few trophoblastic cells, almost all belonging to the cytotrophoblast and only very few to the syncytiotrophoblast, in nearly all specimens investigated (first trimester 10/10, second trimester 5/5, third trimester 4/5). First trimester trophoblast exhibited increased expression of p53 protein in the juxtastromal areas of cytotrophoblast cell islands and columns, that is, in areas where high proliferative activity and increased expression of the epidermal growth factor receptor have been described in the literature. Staining was also occasionally seen in trophoblast invading the myometrium. It is most likely that immunohistochemically detectable expression of p53 protein in the trophoblast is due not to mutation of the gene, as in malignant tumours, but rather to up-regulation of the p53 tumour suppressor gene, which could be a mechanism for controlling trophoblast proliferation.
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PMID:Expression of the p53 tumour suppressor gene in human placenta: an immunohistochemical study. 771 22

Archival biopsy specimens from transitional cell bladder tumours (n = 185) were analysed immunohistochemically for expression of c-myc protein. The results were compared with histopathological and clinical parameters and survival. Forty-three per cent of the tumours were negative for c-myc protein and weak, moderate, or strong cytoplasmic expression was found in 34, 14, and 9 per cent of cases, respectively. Nuclear positivity for c-myc protein was detected in 35 per cent of tumours and nuclear positivity was related to overexpression of c-erb B-2 (P = 0.01) and a high proportion of nuclei were also positive for p53 oncoprotein (p < 0.05). Cytoplasmic expression of c-myc protein was related to histological grade (P = 0.005), papillary status (P = 0.007), the S-phase fraction (P = 0.008), the mitotic index (P = 0.021), overexpression of epidermal growth factor receptor (P = 0.045), and c-erb B-2 (P = 0.17). Expression of c-myc protein was not significantly related to the progression of tumours and it had no prognostic value in survival analysis. Independent predictors were the T-category (P < 0.001), papillary status. (P = 0.001), and S-phase fraction (P = 0.061). The results show that while c-myc gene product participates in growth regulation of human bladder cancer cells, it has no independent prognostic significance.
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PMID:Expression of c-myc protein is related to cell proliferation and expression of growth factor receptors in transitional cell bladder cancer. 773 16

Neuroblastoma, a tumor of the sympathetic nervous system, is one of the most common solid malignancies in infants and represents 7% of all cases of childhood cancer outside of the central nervous system. Thirty-five samples of neuroblastoma from 31 patients were obtained from Duke University Medical Center between 1979 and 1991 and studied to determine the relative prognostic value of a number of clinical, histologic, nuclear, and oncogenic features. The features studied were: stage, Shimada classification, DNA ploidy, MIB-1-proliferation index and status for HER-2/neu, p53 and epidermal growth factor receptor (EGFr). Only age (P = .03), HER-2/neu (P = .01), and p53 (P = .02) reached statistical significance as prognostic indicators. The median survival for patients with HER-2/neu expression was 12 months; median survival for patients with no HER-2/neu expression was 138 months. Similarly, the median survival for patients with p53 expression was 12 months; patients with no p53 expression had a median survival was 144 months. The combination of either HER-2/neu or p53 positivity was especially strong as a prognostic indicator (P = .002).
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PMID:Prognostic indicators for neuroblastoma: stage, grade, DNA ploidy, MIB-1-proliferation index, p53, HER-2/neu and EGFr--a survival study. 774 72

Gene expression of growth factors including epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha), epidermal growth factor receptor (EGFR), oncogenes such as c-myc, N-ras, c-erbB2 and tumor suppressor gene P53 were studied in 4 human lung cancer cell lines using Northern blot technique. Among these cell lines were 2 adenocarcinoma cell lines, one large cell carcinoma cell line and one small cell carcinoma cell line. Expression of EGF and TGF alpha mRNAs were found in all 4 cell lines and EFGR mRNA was seen in 3 out of 4 cell lines. Among these cell lines, 2 cell lines with weaker expression of EGF and TGF alpha, expressed c-myc mRNA. Another 2 cell lines had no c-myc but expressed large amounts of EGF and TGF alpha mRNA. No expression of N-ras, c-erbB2 and p53 were found in these cell lines. The results indicate the presence of autocrine loop of growth factors in these cancer cells. The autostimulation of growth factors may be the main cause for the uncontrolled growth of cancer cells. After treating the cancer cells with EGF, anti-EGF and anti-EGFR antibodies, EGF was found to exert a mild stimulating effect on the growth of one cell line, but no effect on the other cell lines. Anti-EGF and anti-EGFR antibodies inhibited the cell growth on all cell lines. These results provided further evidence for the presence of autocrine loop of growth factors in these lung cancer cell lines.
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PMID:[Gene expression of growth factors, growth factor receptor and oncogenes in human lung cancer cell lines]. 778 Nov 11

Archival biopsy specimens from transitional-cell bladder cancers (n = 222) were analysed immunohisto-chemically for expression of retinoblastoma (Rb) gene protein. The intensity of staining for Rb protein and the fraction of positive nuclei were analysed and related to several other prognostic factors and survival. Six per cent of the tumours were totally negative for Rb protein and abnormal (weak) expression was found in 40% of cases. The fraction of positive nuclei and abnormal expression (weak) were highly significantly interrelated (P < 0.0001). A low value for the fraction of Rb-protein-positive nuclei was related to a large fraction in S phase (P = 0.001), high mitotic index (P = 0.016) and overexpression of epidermal growth factor receptor (P = 0.034) and p53 protein (P = 0.019). A normal Rb protein expression pattern was related to low S-phase values (P = 0.0001) whereas over-expression of p53 was related to high S-phase values (P = 0.0077). Morphometrically measured nuclear atypia and the fraction of Rb-protein-positive nuclei were negatively correlated (P < 0.05). In univariate survival analysis altered expression of Rb protein (P = 0.07) and low frequency (< or = 50%) of Rb-protein-positive nuclei (P = 0.0128) predicted a poor outcome. In a multivariate analysis, reduced expression of Rb protein had no independent prognostic value over T category, papillary status and the size of the S-phase fraction. The results show that tumor-suppressor genes Rb and p53 participate in the growth regulation of human bladder cancer cells in vivo and accordingly modify the prognosis.
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PMID:Reduced expression of retinoblastoma (Rb) gene protein is related to cell proliferation and prognosis in transitional-cell bladder cancer. 786 Jun 18

Although both spatial and temporal heterogeneity confound the description of the genetic events underlying glioma tumorigenesis, it is becoming evident that chromosome 17 loss and p53 inactivating mutations are probably involved early in the pathway of tumorigenesis of some, but not all, astrocytomas. Chromosome 10 loss and epidermal growth factor receptor amplification are seen predominantly in high-grade lesions, although they have not been shown to be independent prognostic indicators. Data is accumulating on the presence of a tumor suppressor gene on chromosome 9p, although the gene remains to be identified. The roles of chromosome 22 and the NF-2 tumor suppressor gene in the tumorigenesis of sporadic and familial meningiomas are discussed here, along with other nonrandom chromosomal alterations that are seen in both astrocytomas and meningiomas.
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PMID:Molecular genetics of astrocytomas and meningiomas. 786 78

New strategies are needed for the detection and treatment of lung cancer and must derive from a fuller understanding of lung carcinogenesis. Frequent molecular genetic abnormalities occur in non-small cell lung cancer (NSCLC), but little is known about which of these precede an invasive carcinoma. We examined the expression of p53, epidermal growth factor receptor (EGFR), and transforming growth factor alpha, the most common molecular genetic abnormalities in NSCLC, in preneoplastic bronchial lesions. Primary NSCLC and associated bronchial lesions were identified by retrospective review of resected tumors at this center. Expression in the invasive carcinomas, the associated bronchial lesions, and normal lung were contrasted using immunohistochemistry. Thirty-four NSCLC associated with 62 bronchial lesions were identified. The invasive tumors included 15 squamous cell carcinomas (SCCs) and 19 non-SCCs. Bronchial lesions included areas of squamous metaplasia (n = 14), inflammatory atypia (n = 19), dysplasia (n = 17), and carcinoma in situ (n = 12). Nineteen (56%) NSCLC and 10 (16%) bronchial lesions exhibited aberrant p53 immunostaining, whereas 18 (53%) NSCLC and 30 (48%) bronchial lesions showed abnormal EGFR immunostaining. Positive staining for transforming growth factor alpha was seen in 16 (47%) NSCLC but occurred inconsistently in the bronchial lesions and in normal bronchial epithelium. Only bronchial lesions associated with squamous cell carcinomas exhibited staining for p53. Aberrant EGFR expression was not associated with a specific type of invasive carcinoma or with specific preneoplastic lesions, although there was a trend toward increased expression in dysplasia and carcinoma in situ relative to metaplasia and atypia. All but one of the NSCLC simultaneously showing aberrant p53 and EGFR staining were SCC. We conclude that: (a) transforming growth factor alpha is variably expressed in normal respiratory epithelium as well as reactive and preneoplastic bronchial lesions; (b) p53 expression is seen in preneoplastic bronchial lesions but is not present in reactive or metaplastic epithelium; (c) aberrant EGFR expression occurs in both reactive and preinvasive bronchial lesions and may be an early marker of neoplastic transformation; and (d) the simultaneous aberrant expression of EGFR and p53 occurs predominantly in SCC and their associated bronchial lesions. These findings indicate that aberrant expression of p53 or the EGFR is frequent in bronchial neoplasia, and coexpression may predispose to the development of squamous cell carcinomas of the lung.
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PMID:Aberrant expression of p53 or the epidermal growth factor receptor is frequent in early bronchial neoplasia and coexpression precedes squamous cell carcinoma development. 788 37

Current basic research on tumorigenesis suggests that the accumulation of multiple genetic defects underlies the progression of initiated cells toward malignancy. Molecular abnormalities associated with primary brain tumors include a wide variety of changes in tumor-suppressor genes, proto-oncogenes and growth factors. A well-known tumor-suppressor gene, p53 gene, is located on the short arm (p) of chromosome 17 and consists of 11 exons transcribed into a 2.2-2.5 kb messenger (m) RNA that encode for a 53 kDa protein. Its alterations are associated with carcinogenesis of astrocytic tumors. Recent evidence suggests also that the p53 protein may function through promoting the expression of the recently discovered gene, WAF1/Cipl. Loss of chromosome 10 was frequently observed in glioblastoma. Southern blot analysis of glioblastomas revealed that 72% have the chromosome 10 loss and that 38% had amplification of the epidermal growth factor receptor (EGFR) gene. Autocrine stimulation of cell growth requires the presence of both growth factors and their receptors. Other genetic alterations in gliomas include elevated expression of the c-myc, Ha-ras, and c-fos oncogenes with a trend to increase in higher malignant grades.
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PMID:Molecular changes involved in the carcinogenesis of brain tumors. 788 30

The authors studied the role of 70-Kd heat shock protein (HSP70) in the progression of breast cancer by examining the correlation between the expression of HSP70 and epidermal growth factor receptor, c-erbB-2, p53, and estrogen receptor in 124 cases of invasive primary human breast cancers. Positivity of an anti-HSP70 monoclonal antibody, C92, was closely associated with the elevation of estrogen receptor (P < .008), whereas it inversely correlated with the expression of p53 (P < .01). In addition, the expression of HSP70 correlated inversely with the expression of epidermal growth factor receptor, although the correlation was not statistically significant (P = .06). These results suggest that the expression of HSP70 plays a role in the progression of human breast cancer.
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PMID:Correlation of heat shock protein 70 expression with estrogen receptor levels in invasive human breast cancer. 790 91


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