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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lung cancer arises after a series of morphological changes, which take several years to progress from normal epithelium to invasive cancer. The morphological changes progress from hyperplasia, to metaplasia, to dysplasia, to carcinoma in situ, to invasive cancer and finally to metastatic cancer. Multiple molecular changes have been documented in lung cancers, both small cell (SCLC) and non-small cell (NSCLC) types. The number of changes has been estimated to be in double digits. These changes include activation of dominant oncogenes myc family, (K-ras and neu genes), as well as loss of recessive growth regulatory genes or anti-oncogenes (p53, and RB as well as unidentified gene or genes on chromosome 3). However, cytogenetic and molecular genetic studies indicate that multiple other specific sites of actual or potential DNA loss may be present in lung cancers. Other changes may include development of drug resistance, and production of growth factors and their receptors. It is tempting to associate specific molecular changes with specific morphological changes, as has been attempted in the colon. However, because of the difficulties in serially sampling the respiratory tract, such studies have not been performed to date. Documentation of molecular changes in premalignant lesions and prospective studies of their prognostic effects will be necessary for the design of rational chemoprevention trials.
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PMID:The molecular biology of lung cancer. 130 9

In the Barrett's oesophagus (BE) progression from metaplasia, via dysplasia, into invasive cancer, an aberrant cell proliferation governed by genetic change plays a central role. Alterations of the p53 tumour-suppressor gene appear especially critical and, like the proliferation marker Ki67, can be detected by immunohistochemistry. The purpose of this study therefore was to investigate the clinical value of p53 and Ki67 as markers for tumour progression in BE, and at the same time test the validity of the concept of a metaplasia-dysplasia-carcinoma sequence in BE by correlating the expression of these markers with various grades of dysplasia. Thirty-two lesions (seven negative for dysplasia, five indefinite for dysplasia, 11 low-grade dysplasia and nine high-grade dysplasia) from 25 archival resection specimens were selected for study. Increasing grades of dysplasia showed increasingly p53 accumulation; p53 accumulation was never observed in mucosa without dysplasia. The increasing p53 expression was accompanied by an increased Ki67-labelling index and an upward shift of the proliferative compartment. The results lend support to the multistep progression model of a metaplasia-dysplasia-carcinoma sequence in BE. Expression of p53 and Ki67, markers which can be easily applied on archival material, can be valuable adjuncts for the histopathological diagnosis of dysplasia and may have predictive value for cancer risk.
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PMID:The value of p53 and Ki67 as markers for tumour progression in the Barrett's dysplasia-carcinoma sequence. 758 89

Intraductal papillary growth of mucin producing hypersecreting, columnar cells characterizes a group of rare pancreatic exocrine neoplasms which we propose to call intraductal papillary-mucinous tumors (IPMT). We analysed the histopathology of 26 IPMT in relation to gastro-enteropancreatic marker expression, genetic changes and biology. Four IPMT showing only mild dysplasia were considered to be adenomas. Nine tumours displayed moderate dysplasia and were regarded as borderline. Severe dysplasia-carcinoma in situ changes were found in 13 IPMT which were therefore classified as intraductal carcinomas. Six of these carcinomas were frankly invasive and two of these had lymph node metastases. The invasive component resembled mucinous non-cystic carcinoma in all but one tumour which showed a ductal invasion pattern. Immunohistochemically, an intestinal marker type was found in most carcinomas, while gastric type differentiation prevailed among adenomas or borderline tumours. K-ras mutations (seven at codon 12 and one at codon 13) were found in 31% of IPMT (2 adenomas, 1 borderline, 5 carcinomas). Nuclear p53 overexpression was detected in 31% of IPMT (6 carcinomas and 2 borderline IPMT) and correlated with p53 mutations (one at exon 8 and the other at exon 5) in two carcinomas. p53 abnormalities were unrelated to K-ras mutation. c-erbB-2 overexpression was observed in 65% of IPMT, with various grades of dysplasia. Twenty-two of 24 patients are alive and well after a mean post-operative follow-up of 41 months. Only two patients, both with invasive cancer at the time of surgery, died of tumour disease. It is concluded that pancreatic IPMT encompass neoplasms which, in general, have a favorable prognosis, but are heterogeneous in regard to grade of dysplasia and marker expression. Adenoma, borderline tumour, intraductal carcinoma and invasive carcinoma can be differentiated. p53 changes but not K-ras mutation or c-erbB-2 overexpression are related to the grade of malignancy. Most IPMT differ in histological structure, marker expression and behaviour from ductal adenocarcinoma.
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PMID:Intraductal papillary-mucinous tumours represent a distinct group of pancreatic neoplasms: an investigation of tumour cell differentiation and K-ras, p53 and c-erbB-2 abnormalities in 26 patients. 782 Mar

Ninety-nine polypoid neoplasms and eight advanced adenocarcinomas of the colon were studied immunohistochemically for p53 protein expression. For reproducible antigen retrieval, formalin-fixed, paraffin-embedded archival sections were heated at 90 degrees C for 120 min in 0.01 mol/L phosphate-buffered saline, pH 7.2, prior to immunostaining. Proliferating cell nuclear antigen served as a positive control marker for effective antigen retrieval. The 99 polyps were categorized into 24 high-grade adenomas, 60 non-invasive cancer-in-adenomas (CIA), and 15 CIA with stromal invasion. All the polyps contained portions of low-grade adenoma. Positive nuclear staining of p53 protein was observed in none of the non-neoplastic mucosa, nine (9%) of 99 low-grade adenomas, 17 (71%) of 24 high-grade adenomas, 46 (77%) of 60 non-invasive CIA, 10 (67%) of 15 invasive CIA, and five (63%) of eight advanced carcinomas. When the antigen retrieval treatment was omitted, the positivity rates were 0, 2, 17, 35, 40, and 63%, respectively. When the antigen-retrieved staining pattern was classified into (i) 'sparse' (< 25% of the nuclei of neoplastic glands labeled), 'scattered' (25-75%) and 'dense' (> 75%); or (ii) 'focal' (the positively labeled glands occupying < 25% of the tumor area), 'intermediate' (25-75%) and 'diffuse' (> 75%), the sparse and focal patterns predominated in high-grade adenomas and non-invasive CIA with low-grade atypia, while the dense and diffuse patterns predominated in invasive CIA and all the advanced carcinomas revealed the dense and diffuse patterns. Non-invasive CIA with high-grade atypia belonged to an intermediate type between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunohistochemical demonstration of p53 protein in colorectal adenomas and adenocarcinomas. Reliable application of the heat-induced antigen retrieval method to formalin-fixed, paraffin-embedded material. 783 78

Squamous epithelial cancer in situ (CIS) of the upper aerodigastric tract is a histopathologically well-defined condition. However, in clinical practice, morphological grading of dysplasia is difficult and shows large variability. The biology of CIS remains enigmatic, and there is yet no reliable way to predict whether a CIS lesion will progress to invasive cancer, remain stable or regress. In the search for markers able to foretell clinical outcome, we performed image DNA cytometry (ICM) and immunohistochemical staining for PCNA as well as p53 in 38 laryngeal CIS lesions, of which 9 progressed to invasive cancer. The majority of the CIS lesions displayed high-grade DNA aberration, a high PCNA-positive rate, and every third lesion was p53-positive by immunostaining. The lesions which progressed to invasive cancer showed a clear tendency towards more pronounced DNA aberration, a higher percentage of intense PCNA staining and more frequent p53 positivity. By combining the results from the analyses of DNA, PCNA and p53 in a prognostic index for each individual case, we correctly classified 82% of the lesions as progressors or non-progressors.
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PMID:Nuclear DNA content, proliferating-cell nuclear antigen (PCNA) and p53 immunostaining in predicting progression of laryngeal cancer in situ lesions. 790 88

The evolution of sequential histological changes from normal cells through invasive cancer affords the cancer biologist the opportunity to identify separate molecular steps involved in cancer progression. As one studies the development of human carcinoma, it becomes apparent that multiple genetic alterations affecting both cellular proto-oncogenes and tumor suppressor genes are involved during the development and progression of both esophageal and gastric cancers. The different histological forms of both esophageal and gastric carcinomas as well as their differing etiologies result in the possibility that a spectrum of genetic changes is involved in different tumor types. p53 abnormalities occur frequently in tumors arising in both organs, and in both sites p53 abnormalities can be observed in precancerous lesions as well as in overt cancer. Subsequent abnormalities affecting other genes (eg, epithelial growth factor receptors [EGFRs]) potentially enhance the growth potential of tumors. This review focuses on abnormalities of oncogenes, tumor suppressor genes, and growth factors commonly found in cancers of the esophagus and stomach.
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PMID:The molecular biology of esophageal and gastric cancer and their precursors: oncogenes, tumor suppressor genes, and growth factors. 792 20

Paraffin embedded material from 15 patients suffering from head and neck squamous cell carcinoma (HNSCC) bordered by dysplastic mucosal areas was immunohistochemically investigated for the presence of p53 protein and Ki-67 proliferation marker. p53 protein was present in 9 cases (60%), invariably in invasive cancer areas as well as in adjacent non-invasive dysplastic mucosa. Only cells exhibiting atypia contained p53 protein. Ki-67 proliferation marker was present in the basal cells of the normal epithelium and more extensive in dysplasias and HNSCC. The presence of Ki-67 closely coincided with p53 protein in the 9 cases exhibiting this. No differences in Ki-67 expression were found between p53 positive and negative cases. It is concluded that the appearance of p53 protein occurs early in carcinogenesis but that cells also may show increased proliferation without involving immunohistochemically detectable alterations in the p53 gene.
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PMID:The presence of p53 protein in relation to Ki-67 as cellular proliferation marker in head and neck squamous cell carcinoma and adjacent dysplastic mucosa. 803 2

To assess potential clinical applications for molecular genetic markers associated with human esophageal tumorigenesis, ten patients with primary esophageal adenocarcinomas were studied prospectively to evaluate expression of the p53 and H-ras genes. Total RNA was extracted from tumor, Barrett's epithelium, and histologically normal esophageal mucosa obtained at surgical resection, and gene expression investigated by Northern blot analysis. p53 was overexpressed, relative to normal tissue from the same patient, in seven tumor and six Barrett's specimens, whereas high levels of H-ras were found in only four tumor and one Barrett's specimen. Clinical correlative data were obtained for all patients, with a median follow-up of 14 months. Advanced pathologic stage was associated with poor survival. No association was found between gene expression and outcome. Three patients with low p53 and H-ras levels developed metastatic disease 7 to 12 months following resection. We conclude that both p53 and ras are implicated in the progression of Barrett's epithelium to invasive cancer, and that further clinical correlative studies are warranted to evaluate potential clinical application for such molecular markers.
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PMID:p53 and ras gene expression in human esophageal cancer and Barrett's epithelium: a prospective study. 807 80

Lung cancer arises after a series of morphological changes, which take several years to progress from normal epithelium to invasive cancer. The morphological changes progress from hyperplasia, to metaplasia, to dysplasia, to carcinoma in situ, to invasive cancer and finally to metastatic cancer. Multiple molecular changes have been documented in lung cancers, both small cell (SCLC) and non-small cell (NSCLC) types. The number of changes has been estimated to be in double digits. How can so many changes develop in one cell? One possible explanation is the "field cancerization" theory, that states that all or much of the aerodigestive tract epithelium has been mutagenized, perhaps as the result of exposure to tobacco products or other carcinogens. The molecular changes include activation of dominant oncogenes (myc family, K-ras and HER/2/neu genes), as well as loss of recessive growth regulatory genes or anti-oncogenes (p53, and rb as well as unidentified gene or genes on chromosome 3). However, cytogenetic and molecular genetic studies indicate that multiple other specific sites of actual or potential DNA loss may be present in lung cancers. Many of the well characterized molecular changes may function as negative prognostic factors for survival in subsets of lung cancers. Other changes may include development of drug resistance, and production of growth factors and their receptors. It is tempting to associate specific molecular changes with specific morphological changes, as has been attempted in the colon. However, because of the difficulties in serially sampling the respiratory tract, only a modest amount of data has been collected to date. It appears that deletions of chromosome 3p, hyperproliferation and aneuploidy are early changes, while p53 mutations appear later in the preneoplastic cascade. Documentation of intermediate markers for lung cancer and prospective studies of their prognostic effects will be necessary for the design of rational chemoprevention trials.
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PMID:The molecular and cellular basis of human lung cancer. 816 65

Noninvasive transitional cell carcinomas of the bladder can have two distinct morphologies suggesting they contain different genetic alterations. Papillary transitional cell carcinomas (T(a) tumors) are often multifocal and only occasionally progress, whereas flat tumors (carcinomas in situ, CIS), frequently progress to invasive disease. We examined 216 bladder tumors of various stages and histopathologies for two genetic alterations previously described to be of importance in bladder tumorigenesis. Loss of heterozygosity of chromosome 9 was observed in 24 of 70 (34%) T(a) tumors but was present in only 3 of 24 (12%) CIS and dysplasia lesions (P = 0.04). In contrast, only 1 of 36 (3%) T(a) tumors contained a p53 gene mutation compared to 15 of 23 (65%) CIS and dysplasias (P < 0.001), a frequency comparable to that observed in muscle invasive tumors (25 of 49; 51%). The presence of p53 mutations in CIS and dysplasia could explain their propensities to progress since these mutations are known to destabilize the genome. Analysis of several tumor pairs involving a CIS and an invasive cancer provided evidence that the chromosome 9 alteration may in some cases be involved in the progression of CIS to more invasive tumors, in addition to its role in the initiation of T(a) tumors. However, the CIS and secondary tumor were found to contain different genetic alterations in some patients suggesting divergent progression pathways. Bladder carcinogenesis may therefore proceed through two distinct genetic alteration pathways responsible for generating superficial tumors with differing morphologies and pathologies.
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PMID:Two molecular pathways to transitional cell carcinoma of the bladder. 830 42


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