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)

Metastatic phenotype in human solid tumors is believed to follow stochastic acquisition of structural genetic aberrations-so-called multistep tumor progression. We tested this hypothesis in breast carcinoma by immunostaining 89 stage-heterogeneous cases for the products of three genes (p53, ERBB-2, and EGFR) which are frequently altered in this tumor system. Variable relationships were observed between advanced disease stage and immunostaining for individual gene products (ERBB-2 - p = 0.05, EGFR - p = 0.02, p53 - p = 0.12, Chi Square test). Regional or distant metastases at presentation correlated with multiple oncogene/tumor suppressor gene expression abnormalities: node negative -59% none positive, 29% one positive, 12% two or more positive, vs. node positive -37% none positive, 23% one positive, 39% two or more positive (p = 0.01). Only 2/12 (17%) of tumors with distant metastases at presentation were negative for abnormal expression of any of these gene products, and 7/12 (58%) were positive for two or three. Among axillary node negative patients who developed recurrences, 67% exhibited staining for at least one gene product, compared to only 27% of those without recurrences (p = 0.02). All 5 cases with abnormal staining for each gene product had regional or distant metastases at presentation and recurred. In multivariate analysis, individual expression of p53 outweighed expression of ERBB-2 and EGFR in correlation with outcome. These data suggest clinical neoplastic progression of breast carcinomas correlates with cumulative genetic events detectable by protein expression. Short term recurrence, however, may correlate more closely with abnormal expression of p53 than with EGFR or ERBB-2.
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PMID:Concurrent abnormal expression of ERBB-2, EGFR, and p53 genes and clinical disease progression of breast carcinoma. 791 62

The evaluation of molecular markers in breast carcinomas can be routinely assessed by (i) histochemistry for ploidy measurement (Feulgen stain) and for AgNORs counts, and by (ii) immunocytochemistry (Ki67, cathepsin D, pHER-2/neu, EGFR, ER, PR, pS2, p53). Immunocytochemical assays are correlated to biochemical assays and are particularly relevant in small tumors in which only small amount of tissue is available. Immunocytochemical assays provide for data additional to current histological methods, useful for prognostic evaluation and for the selection of node negative patients who may benefit from adjuvant therapy. Nevertheless, immunocytochemical assays can be used for clinical purposes only if they are standardized (frozen sections, image analysis).
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PMID:[Molecular markers in breast cancer: practical aspects and morphologic evaluation]. 807 88

Almost all atypical epithelial lesions of the stomach consist of atypical cells in the superficial part of the glands and nonatypical cells in the deeper portion of the glands. A transition zone was formed between the superficial atypical gland cells and the deeper nonatypical gland cells. Positive cells were widely demonstrated with immunohistochemical stains for PCNA in the superficial atypical glands and transition zone. The rate of PCNA positivity was 37.7%. However, a small number of positive cells for EGFR (8.5%), c-erbB-2(11.3%), p53(11.3%) and c-K-ras(1.7%) were found in ATP. The incidence of positivity for these factors was low compared with that for carcinomas. The percentages of positive cells for EGFR(1.5%) and c-erbB-2(4.5%) were very low in intestinal metaplasia.
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PMID:[Immunohistochemical study for growth factor and oncogene on atypical epithelium of the stomach]. 810 26

Immunohistochemical staining for EGF, EGFR, c-erbB-2, p53, K-ras and PCNA was performed on the formalin-fixed, paraffin embedded sections of resected gastric carcinomas. A relatively high positive rate was observed for EGFR and c-erbB-2 in the well-differentiated adenocarcinomas and p53 in the poorly-differentiated adenocarcinomas. The positive rate of these factor was higher in the advanced cases than in the early cases, and also in the deep invasive area than the superficial area. According to the PCNA staining, a relatively high positive rate was observed in the well-differentiated adenocarcinomas compared with the early cases of poorly-differentiated adenocarcinomas, but the positive rate was markedly higher in the advanced cases of the latter. Typical signet-ring cell carcinomas showed the lowest positivity rate compared with the other histological types of gastric carcinomas.
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PMID:[Immunohistochemical study of growth factors and oncogenes in gastric carcinomas]. 810 27

Activation of cellular or c-oncogenes and loss of function of suppressor genes appears to be the key event in the formation of most human cancers. Altered forms of these genes or their protein products have the potential to provide a new generation of cancer markers. As cancer markers, the most useful application of c-oncogenes and suppressor genes so far, has been in providing prognostic information. The correlation of N-myc gene amplification with poor prognosis in neuroblastoma was one of the first examples of prognostic data supplied by a c-oncogene. Most, but not all investigators, find that either amplification or increased expression of c-erbB-2 gene correlates with poor prognosis in breast cancer. Other potential prognostic markers in breast cancer include amplification of the c-myc gene, and increased expression of both EGFR and p53 protein. Although c-oncogenes and suppressor genes have the potential to supply prognostic information in a broad range of cancers, many of the results are still preliminary with conflicting conclusions.
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PMID:Cellular oncogenes and suppressor genes as prognostic markers in cancer. 812 58

Breast cancer is a complex but increasingly well-understood disease. Clearly, multiple alterations from normal mammary cells are required to achieve a transformed phenotype. Furthermore, there may be several possible alterations within broad categories that will produce the transformations leading to the malignant state. The specific set of alterations within a given cancer may thus provide necessary information about how it is unique and how it may best be treated. Several of the newer biologic markers of breast cancer may provide very specific treatment information. erbB-2 may predict for improved response to doxorubicin, rather than CMF. hsp 27 may predict for failure of doxorubicin. pS2 or EGFR may provide supplemental information predicting response to hormonal therapy. Each of these variables has strong evidence to support its use in this manner, but that evidence has been obtained on limited numbers of patients treated in a limited number of ways. The most established markers, with multiple studies indicating their prognostic benefit, are erbB-2, cathepsin D, and proliferation markers. Of the several proliferation markers there may be no one choice that is best. However, very clearly, any marker must be carefully assessed for appropriate cut-off values, and cut-off values established by one cohort of patients should be verified against another cohort of patients. The oncoproteins associated with cell cycle regulation (cyclin D, p53, Rb, and c-myc) have shown strong promise of providing important prognostic information. The limited studies to date indicate that these markers are independent of one another. Cell cycle regulation may be an area in which any defect may serve to deregulate the cell, and therefore several defects in one cell would be unlikely. The specific nature of the defect in a given cancer may be very important. With the advent of immunohistochemical methods to measure most of the markers, more information may become available. Finally, the burgeoning area of tumor-stromal interactions is replete with potentially important markers of cancer prognosis. The growth factors, which are marginally a part of this area owing to the probable importance of paracrine effects on cancer cell growth, have progressively developed a body of literature supporting their prognostic potential. However, they have rarely been studied in conjunction with the other aspects of tumor-stromal cooperation. The markers of metastatic potential, nm23 and angiogenesis, have been shown in small cohorts to have considerable prognostic import.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Overview of the biologic markers of breast cancer. 815 Jul 84

The effects of regional heterogeneity on the accuracy of histological grading of gliomas are well known, but little has been reported about its implications for other diagnostic modalities. This study investigated the relationships of regional heterogeneity in tumor proliferative activity, measured by Ki-67 labeling indices (LI), and histological grades for 16 regionally sampled glioma resections. There was a strong correlation between histological grades and Ki-67 LI in individual regions (p < 0.001), and both methods demonstrated comparable heterogeneity. Heterogeneity increased with tumor grade, probably as an expression of the increased genetic instability that accompanies tumor progression. Similarly, regions with comparable proliferative activity tended to cluster, paralleling clonal expansion. Thus, both histological grading and Ki-67 LI are subject to heterogeneity-induced sampling errors that limit their diagnostic accuracy, particularly in small biopsies. However, fewer grading errors occurred when using both methods together than when using either method alone, suggesting that the use of multiple techniques may reduce the adverse effects of regional heterogeneity on diagnostic accuracy. Regional heterogeneity appears to be a ubiquitous feature of gliomas: it also has been reported in karyotype, p53 oncogene mutations, and PDGF and EGFR expression. The effects of regional heterogeneity on new methods for studying gliomas need to be considered.
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PMID:Regional heterogeneity in the proliferative activity of human gliomas as measured by the Ki-67 labeling index. 822 80

Recent publications dealing with the pathology of squamous carcinomas of the head and neck have been critically reviewed with particular reference to potential prognostic factors and improved methods for identifying nodal metastases. The topics covered include cytophotometry and proliferative patterns, molecular biology (EGFR and p53 genes), cell adhesion molecules (E cadherin), and combined radiologic and pathologic approaches to detect small volume metastases in cervical lymph nodes.
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PMID:Pathology of squamous carcinomas of the head and neck. 849 10

DNA derived from medulloblastoma biopsies was analyzed to determine if deletions of the 17p region, mutations of the TP53 gene, or amplification of the c-myc, N-myc, EGFR (epidermal growth factor receptor), or MDM2 (murine double-minute-2) genes was indicative of a poor prognosis. Loss of heterozygosity for 17p, observed in 8/28 (29%) paired samples, was associated with a shortened survival period (p = 0.045 by the logrank test). TP53 mutations occurred in 2/46 (4.3%) tumor samples. c-myc Amplification was seen in 3/43 (6.9%) cases, while none of the tumors contained amplified N-myc, EGFR, or MDM2 genes. These results demonstrate that, while only rare medulloblastomas contain TP53 gene mutations or amplification of the c-myc gene, loss of heterozygosity on chromosome 17p is indicative of a significantly worse prognosis among patients with these tumors. Further, these results provide a strong impetus for a prospective analysis of loss of heterozygosity in a cooperative group setting, which would include tumor staging, a selection of treatment modalities, and multivariate analyses.
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PMID:Prognostic implications of chromosome 17p deletions in human medulloblastomas. 852 74

Recent advances in molecular genetics have disclosed oncogenes playing a significant role in the development of malignant gliomas. Amplification of the c-erb gene which code EGFR and aberration of P53 oncogene play a significant role in the development of most malignant gliomas. Karyotype analysis of malignant gliomas revealed gains of chromosome 7, loss of chromosome 10, double minutes and loss of heterozygosity. The development of the tumors appear to result from the accumulation of those multiple genetic alterations. Although many cases of familiar malignant gliomas have been reported the role of hereditary factors in familial transmission still remains controversial. Chromosomal abnormalities seemed to be confined to the tumor cell, and no alteration in karyotype of peripheral blood, which indicated germ line mutation, was demonstrated. However, several authors indicated that the frequency of malignant gliomas in the relatives of patients was estimated more than ten times to the controls. Some hereditary factors might play a role in malignant gliomas.
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PMID:[Malignant glioma]. 853 25


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