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)

Since the nuclear accumulation of p53 protein is known to correspond well with mutation of the p53 tumor suppressor gene, the authors examined 88 primary lung cancer specimens immunohistochemically using anti-p53 mouse monoclonal antibody, pAb1801, and analyzed the relationship between the immunohistochemical results and clinicopathological features. Nuclear localization of p53 protein was found in 43/88 (49%) tumor specimens, but not in the corresponding normal lung tissues. The percentage of cases showing nuclear p53 localization varied according to the histological type. In squamous cell carcinoma, nuclear p53 localization was found in 15/26 (57%), appearing more frequently than in other histologic types. However, no obvious correlation was observed between nuclear p53 localization and patients' age, sex, history of smoking, TNM factor, degree of differentiation, or any other clinicopathological features analyzed. In adenocarcinoma, nuclear p53 localization was found in 20/46 (43%). Incidence of positive cases was significantly correlated with regional lymph node metastasis, distant metastasis, and pathological stage (P less than 0.05). These results indicate that mutation of the p53 tumor suppressor gene plays an important role in the development of primary lung cancer, and that nuclear accumulation of p53 protein is a potential prognostic factor in adenocarcinoma of the lung.
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PMID:Clinicopathological significance of nuclear accumulation of tumor suppressor gene p53 product in primary lung cancer. 154 66

This chapter has briefly reviewed the development and progression of peripheral-type adenocarcinoma of the lung, focusing particularly on bronchioloalveolar carcinoma consisting of the nonmucus-producing cell type with or without sclerosis. Histoloical examination reveals that scar cancers are rare except in cases of diffuse pulmonary fibrosis and that many nonmucus-producing bronchioloalveolar carcinomas appear to develop from atypical adenomatous hyperplasia, which can be called adenoma or very well-differentiated adenocarcinoma, and to progress stepwise. Stepwise progression in malignancy can be disclosed not only by cytological and histological examination but also by proliferative activity of the tumor, such as mitotic activity, the percentage of DNA-synthesizing cells and the frequency of proliferating cell nuclear antigen-positive cells, the mean nuclear DNA content of tumor cells and occurrence of aneuploid cell lines, and abnormalities of oncogenes (c-Ki-ras, myc family, and c-erbB2), such as point mutation, rearrangement, amplification, and tumor suppressor genes (point mutation and deletion) such as p53.
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PMID:The development and progression of adenocarcinoma of the lung. 770 84

Atypical alveolar hyperplasia (AAH) has recently been described in human lungs in association with primary lung cancer, particularly adenocarcinoma. Unlike proximal bronchogenic carcinoma, peripheral (parenchymal) adenocarcinoma of the lung does not have a well-recognized progenitor lesion. Epidemiological morphometric, and cytofluorometric data in the literature suggest that AAH is a candidate premalignant entity. In this study, 97 AAH lesions were found in lungs resected from 29 patients (1-13 lesions per case, mean 3.5) being treated for presumed carcinoma (25/29 had adenocarcinoma). From a study case-load of 285 adenocarcinoma-bearing lungs, the AAH incidence was 8.8 per cent. Sections of 67 AAH lesions from 19 patients were stained using monoclonal antibodies against Ki67 (MIB1), p53 (DO7), and c-erbB-2 (NCL-CB11). Ki67 was expressed in up to 10 per cent of AAH nuclei. Thirty-nine lesions (58 per cent) showed stainable p53 protein, while five (7 per cent) expressed membrane c-erbB-2 oncoprotein. These latter five lesions were all strongly positive for p53, and both p53 and c-erbB staining was associated with increased cellular crowding and pleomorphism in AAH. These data demonstrate that AAH exhibits some genetic changes associated with malignancy and thereby support the hypothesis that AAH is premalignant.
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PMID:Atypical alveolar hyperplasia: relationship with pulmonary adenocarcinoma, p53, and c-erbB-2 expression. 788 86

The development of human adenocarcinoma of the lung involves multiple genetic changes including activation of oncogenes and loss of tumor suppressor genes. Patients whose lung tumors contain K-ras oncogene mutation, accumulation of the protein product of the tumor suppressor gene p53, or erbB-2/neu oncoprotein overexpression have been shown to have a worse prognosis. We examined these three genetic indicators in 29 lung adenocarcinomas to determine whether these markers are present in the same tumors or if they represent molecular changes that define different subsets of patients. P53 nuclear protein accumulation and erbB-2/neu protein overexpression were determined by immunohistochemical analysis of cryostat sections of tumor specimens and corresponding normal lung tissue. K-ras mutations were detected by radiolabeled oligonucleotide probes, specific for the various twelfth codon mutations, hybridized to exon 1 of K-ras, which was amplified by the polymerase chain reaction. Increased nuclear accumulation of p53 protein was found in 11 adenocarcinomas (38%). All of the p53 positive tumors were found to show high level staining and homogeneous expression of erbB-2/neu protein. K-ras mutations were detected in seven tumors (24%), all of which overexpressed erbB-2/neu. The presence of a K-ras mutation did not correlate with p53 accumulation. In total, 93% of the tumors were found to overexpress erbB-2/neu, the highest being in one tumor with erbB-2/neu gene amplification. The presence of K-ras twelfth codon mutation was associated with increased cigarette smoking. In conclusion, erbB-2/neu overexpression is a common event in lung adenocarcinomas. Furthermore, the presence of K-ras mutation and p53 protein accumulation define separate groups of patients. The mechanisms by which these genetic alterations interact or adversely affect prognosis is unknown.
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PMID:Alterations of K-ras, p53, and erbB-2/neu in human lung adenocarcinomas. 790 43

Histological examination revealed that many peripheral type papillary adenocarcinomas appear to develop from atypical adenomatous hyperplasia (AAH), which can be called adenoma or in situ adenocarcinoma, and progress stepwise. Molecular-biologically, loss of heterozygosities of 3, 11 and 17 chromosomes, point mutation of ras oncogene and p53 anti-oncogene, amplification of myc oncogene, and overexpression of erbB2 oncogene are related to lung cancer development. Especially, ras and p53 gene abnormalities are closely associated with poor prognosis of lung adenocarcinoma. Future molecular-biological examinations should focus on AAH and/or early stage adenocarcinoma of the lung, in order to clarify the gene abnormality at the early stage of lung carcinogenesis.
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PMID:[Advances in pathobiological research on lung carcinoma]. 797 12

I examined 15 cases of differentiated adenocarcinoma of the lung which showed mutation of the p53 gene and whose primary lesions could be divided into three components (peripheral component, intermediate component and central component). Mutation of the p53 gene in each component was examined by an immunohistochemical method and polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) analysis in order to elucidate the correlation between histological types in the adenocarcinoma and mutation of the p53 gene. Furthermore, immunohistochemical detection of Ki-67 antigen and the ploidy pattern were examined for each component of the primary lesions and metastatic lesions. As a result, mutation of the p53 gene was detected mainly in the intermediate and central components, that is, in 13 cases in the intermediate component and in all cases in the central component. Higher proliferative activity as well as a DNA aneuploidy pattern were seen in these areas. In contrast, the peripheral component showed mutation of the p53 genes in only 4 cases. Lower proliferative activity and a normal diploidy pattern were seen in this area. As for the metastatic lesions, mutations of the p53 gene were detected in the metastasis of the lymph nodes and brain, as well as in the intermediate and central components of the primary lesions. Moreover, these metastatic lesions showed a higher proliferative activity which was similar index to the central or intermediate one. In 2 cases the metastasis of the lymph node showed an aneuploidy pattern as well as the intermediate and central components.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A correlation between mutation of the p53 gene and histological heterogeneity in differentiated adenocarcinomas of the lung, with reference to stepwise progression and metastatic ability. 801 71

The Johns Hopkins Lung Project developed an archive of sputum specimens during a randomized trial of lung cancer screening (1974-1982). We identified 15 patients from that trial who later developed adenocarcinoma of the lung. The primary lung carcinomas from 10 of these 15 patients contained either a ras or a p53 gene mutation. Using a polymerase chain reaction-based assay, stored sputum samples obtained prior to clinical diagnosis were examined for the presence of these same oncogene mutations. In 8 of 10 patients, the identical mutation identified in the primary tumor was also detected in at least one sputum sample. The earliest detection of a clonal population of cancer cells in sputum was in a sample obtained more than 1 year prior to clinical diagnosis. These results provide the basis of a novel approach for detection of lung cancer based on the evolving molecular genetics of this disease.
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PMID:Detection of oncogene mutations in sputum precedes diagnosis of lung cancer. 813 72

The topographical distribution of a mutation provides insight into past patterns of tumor evolution. This approach was applied to two loci commonly mutated in adenocarcinoma of the lung--p53 and c-K-ras. In 41 primary adenocarcinomas, c-K-ras codon 12 point mutations were detected in 8 (19.5%) tumors and p53 point mutations were detected in 10 (24.4%) tumors, with one tumor harboring both mutations. These mutations were only detected in malignant cells and with a homogeneous topographical distribution throughout 16 tumors, including metastasis. Intratumor heterogeneity was detected in only one tumor in which a small portion lacked the specific p53 mutation. Based on this topographical analysis, it is likely that when these mutations occur in adenocarcinoma of the lung, they are usually acquired during the very earliest phases of tumor formation before the bulk of clonal expansion, and in very small precursor lesions.
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PMID:c-k-ras and p53 mutations occur very early in adenocarcinoma of the lung. 831 Nov 14

When solitary pulmonary tumors are observed in patients with a history of cancer, differentiation between metastasis and primary lung cancer is crucial for appropriate therapy. Assuming that p53 mutations are conserved in metastases, mutation analysis of the p53 gene would be a valuable tool in differentiating metastases from primary carcinomas of the lung. In nine of 267 resected lung tumors, the origin of the lung tumor could not be defined histologically. Five patients had a history of colorectal carcinoma, one had a history of breast carcinoma, one had a history of soft-tissue carcinoma, and one had a history of head and neck carcinoma. One patient with a clear cell carcinoma of the lung had been surgically treated for both renal and thyroid cancer. Material from one patient with adenocarcinoma of the lung, histologically defined regional lymph nodes, and distant brain metastasis served as a control. We extracted deoxyribonucleic acid from the snap-frozen tissue of the unclassified lung tumors, from paraffin-embedded tissue of the previously removed primary cancers, and also from peripheral blood of the patients. Exons 2 to 11 of the p53 gene were amplified in separated polymerase chain reactions and directly sequenced. In all cases, the presence of germline mutations was excluded by analysis of peripheral blood deoxyribonucleic acid. The p53 mutation detected in the deoxyribonucleic acid of the lung tumor of the control patient proved to be conserved in the lymph nodes as well as in the brain metastasis. In two cases, the lung tumors exhibited a p53 mutation not present in the previously removed primary tumor and were therefore classified as new primary lung cancers. In five cases, the lung tumors proved to be metastases of the first tumor, exhibiting the identical p53 mutation. One of these lung tumor samples could be identified as a metastasis from the renal cancer, but the corresponding thyroid cancer material was different. For two cases, molecular analysis remained inconclusive. In one case, no p53 mutation could be found in the compared samples; in the other, no deoxyribonucleic acid could be extracted. Analysis of p53 mutations allowed exact classification in tumors for which standard methods failed to distinguish between metastasis or primary tumor. More than two thirds of lung tumors in patients with previous gastrointestinal carcinoma were revealed to be metastases, but second primary lung cancer could also be diagnosed. This diagnosis allowed correct surgical and adjuvant treatment of these patients.
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PMID:Molecular genetic differentiation between primary lung cancers and lung metastases of other tumors. 861 43

In order to ascertain the feasibility of detecting p53 gene mutations in patients with lung cancer in a nonsurgical diagnostic setting before starting treatment, we screened for p53 gene mutations in tumor specimens obtained using diagnostic methods such as fiberoptic bronchoscopy, thoracentesis, and percutaneous needle aspiration. We examined 206 specimens from 66 patients diagnosed with primary lung cancer at Hiroshima University Hospital between October 1991 and July 1993 using the polymerase chain reaction/denaturing gradient gel electrophoresis technique. p53 gene mutations were found in 64 of 159 (40%) cytologically positive specimens, but in none of 47 cytologically negative specimens. The PCR-based assay did not increase the sensitivity of the cytopathologic examination in detecting malignant cells. The type and location of the p53 gene mutation was the same in cytologically positive specimens obtained by different methods, but from the same patient. Of the 66 patients, p53 gene mutations were found in 27 (41%) at the time of the first nonsurgical diagnostic examination: 7 of 12 (58%) with small cell carcinoma, 9 of 20 (45%) with squamous cell carcinoma, and 11 of 34 (32%) with adenocarcinoma of the lung. The incidence of p53 gene mutation for each histologic subtype was comparable to previously published data examining surgically and/or autopsy-obtained specimens. These results indicate that detection of p53 gene mutations in a nonsurgical, diagnostic setting is feasible. This technique will make it possible to assess the significance of p53 gene mutations in relation to survival and response to therapy before starting treatment, in future prospective studies.
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PMID:Detection of p53 gene mutations in cytopathology and biopsy specimens from patients with lung cancer. 888 16


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