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)

We studied the expression of p53 gene product in pancreatic adenocarcinomas of the usual ductal type to determine its relationship to cigarette smoking and its usefulness as an independent prognostic indicator. Twenty-six resection specimens of pancreatic adenocarcinoma were examined by immunohistochemistry using an antigen retrieval solution and monoclonal PAb1801 and polyclonal CM1 antibodies on paraffin-embedded material. Specific nuclear p53 expression for both PAb1801 and CM1 was identified in seven cases (27%). In all cases immunoreaction was confined to neoplastic cells. Three of four (75%) tumors from patients who had never smoked showed immunoreaction, whereas only three of 14 (21%) tumors from smokers showed positive staining. Cases with positive staining had shorter mean survival (6.3 mo) than cases that failed to stain (9.8 mo), but the difference was not statistically significant in this small study. There was no statistically significant association between p53 immunoreactivity and other clinicopathologic parameters. Our findings indicate that abnormalities of p53 gene in pancreatic adenocarcinomas may not be directly related to cigarette smoking. Those patients who survived the longest tended to have tumors negative for p53 immunostaining. p53 immunoreaction may be a useful feature in distinguishing adenocarcinoma from chronic pancreatitis in small biopsies.
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PMID:Expression of p53 protein in pancreatic adenocarcinoma. Relationship to cigaret smoking. 764 71

The expression of oncoprotein, tumor suppressor gene, cellular proliferation and differentiation markers were studied in 64 malignant and benign pancreatic tumors, adjacent and distant to the tumor duct epithelium. Activity of these markers was compared to 16 cases of chronic pancreatitis. Tumor suppressor gene p53 and transforming growth factor alpha were overexpressed in the majority of malignant tumors. The expression of c-erbB-2 oncoprotein and cellular proliferation marker Ki67 was less common in malignant lesions, but was absent in the benign cases. The positive staining of all markers in ductal epithelium outside of the tumor, particularly in pancreatic duct carcinoma, suggest the ductal histogenesis of this malignancy. The presence of c-erbB-2 and Ki67 in malignant lesions only suggest their possible use in the differentiation of pancreatic malignancies and chronic pancreatitis.
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PMID:Expression of p53 tumor suppressor gene, oncoprotein c-erbB-2, cellular proliferation and differentiation in malignant and benign pancreatic lesions. 784 27

The bad prognosis of exocrine pancreas carcinoma manifests itself by a high incidence of recidivation, early metastasis formation and a low 5-year survival rate of 1-2% on an average has not essentially been improved in recent times although progress is evident in diagnosis as well as in surgical, radiological and cytostatic therapy. The unfavourable course of illnesses is due to the symptomless early phase rather than the existing diagnostic potential. Thus, a recording, standardization and definition of pancreatic duct atypias is a necessity for optimizing the pattern of examinations. Topographically, the structure of pancreatic parenchyma may be classified by 1) interlobular ducts; 2) intralobular ducts; 3) intercalated ducts; 4) centroacinar cells, and 5) acinar cells. Based on this matrix, entities of varying diagnostic relevance may be derived, i.e. 1) orthological histiomorphological tissue formations; 2) hyperplastic epithelial changes; 3) metaplastic epithelial formations; and 4) atypical hyperplasias. Beyond this, there are numerous indications of a redifferentiation of numerous pancreatic cell types, primarily of acinar cells. The close relationships between ductal and acinar cells may be subsumed as a terminal ductulo-acinar intercalated duct complex. Against the background of chronic pancreatitis and corresponding length of history (< 6.5 years), cancer may develop in up to 16% of cases. On the molecularbiological level, point mutations of the K-ras gene, a mutation or deletion of the p53 suppressor gene and an excess production of the c-erbB-2 protooncogene are found in a great number of pancreatic carcinomas.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Lesions of the pancreatic duct epithelium and histogenesis of exocrine pancreatic carcinomas]. 794 29

Heat shock proteins (hsp) are involved in degradation or chaperoning nascent and abnormal proteins to various subcellular locations. p53 tumour suppressor gene overexpression and mutation occur frequently in pancreatic cancers. Mutant p53 proteins produced in cancers of other sites have been found to form complexes with hsp 70. Consequently, binding to hsp 70 may be used to indicate the presence of mutant p53 proteins. The presence of hsp 70 was investigated by immunohistochemistry in core biopsies of 42 adenocarcinomas of the pancreas (well differentiated, N = 1 and moderate to poorly differentiated, N = 41). Four cases of islet cell tumours were included in the study. These neoplasias were compared with biopsies of chronic pancreatitis (N = 9) and normal pancreas (N = 5). The majority of adenocarcinomas, 24/42 (57%), showed expression of both hsp 70 and p53. None of the islet cell tumours or cases of chronic pancreatitis showed p53 and hsp 70 coexpression. Only 1 (20%) of the normal pancreas showed concurrent nuclear immunostaining for p53 and cytoplasmic immunostaining for hsp 70. The high proportion of pancreatic adenocarcinoma showing immunoreactivity for both hsp 70 and p53 may indicate high mutation rate of the p53 gene in this tumour. Further studies using molecular techniques are required to elucidate the nature of both hsp and p53 genes in pancreatic cancers.
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PMID:Overexpression of heat shock protein (hsp) 70 associated with abnormal p53 expression in cancer of the pancreas. 794 33

The p53 tumour suppressor gene and its protein products after point mutations are currently attracting wide attention in the investigation of human tumours. In this study we present the findings on percutaneous pancreatic biopsies of 82 cases after routine processing and immunostaining for the polyclonal p53 antibody CM1, an antibody directed against both wild and mutant forms of p53 protein. There were 51 carcinomas, 5 islet cell tumours, 16 cases of chronic pancreatitis (including one with atypical ductal epithelium) and seven histologically normal pancreatic biopsy specimens. None of the seven normal cases showed any definite nuclear immunostaining for p53. Thirty-two (63%) of the pancreatic adenocarcinomas showed moderate to intense immunoreactivity. Of the 16 cases of chronic pancreatitis, 11 were negative and three showed equivocal immunostaining. The one case with ductal epithelial atypia showed mild to moderate immunoreactivity. All islet cell tumours were negative. The expression of the p53 gene, therefore, appears increased in the majority of pancreatic adenocarcinomas while this is not observed in chronic pancreatitis or normal pancreatic tissue. Nuclear immunoreactivity for p53 protein may represent mutant forms because of the short half-life of the wild-type protein. The lack of p53 expression in some cases of pancreatic adenocarcinoma may be due to different types of mutant proteins not detectable by the CM1 antibody. Nuclear immunoreactivity to the p53 protein in pancreatic biopsy is more suggestive of a malignant tumour than chronic pancreatitis.
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PMID:Immunohistochemical demonstration of the p53 tumour suppressor gene product in cancer of the pancreas and chronic pancreatitis. 821 96

Pancreatic expression of the p53 tumor suppressor gene was studied in pancreatic adenocarcinomas and chronic pancreatitis. By immunohistochemistry, 16 of 34 (47%) cancers and none of the 24 chronic pancreatitis samples revealed nuclear staining. Sequence analysis indicated that 8 of 24 (33%) cancers were mutated for the p53 gene. Point substitutions occurred at codons 35, 105, 133, 213, 213, 258, and 299. A three base-pair in-frame insertion was identified between codons 261 and 262. None of 8 chronic pancreatitis samples exhibited p53 gene mutations. These data support a role for p53 gene alterations in human pancreatic cancer, and suggest that loss of its regulatory functions may constitute one of the differences between pancreatic cancer and chronic pancreatitis.
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PMID:p53 mutations are common in pancreatic cancer and are absent in chronic pancreatitis. 851 40

There are approximately 27,000 new cases of carcinoma of the pancreas each year and most afflicted patients will die of the disease. Although smoking is a common denominator, chronic pancreatitis is considered an important precursor lesion in a smaller number of cancers. Pancreatic cancer is primarily a disease of the pancreatic ducts. The molecular events are under intense study, but c-K-ras mutation is involved in approximately 80% of the cases and p53 to a slightly lesser degree (60-80%). Early manifestations are usually occult, but jaundice is a common manifestation in patients with cancers of the pancreatic head. Thin-slice computed tomography, portography, and endoscopic retrograde cholangiopancreatography are currently the most sensitive detection techniques. The developing use of endoscopic ultrasound and laparoscopy appear to enhance detection and are under evaluation. In many patients with advanced disease, endoscopic bypass may eliminate the need for unnecessary surgery, although gastrointestinal bypass is still required in some patients (10-15%). Curative resection is possible in selected patients (perhaps 10-15%), with expectation of extended survival ranging from 6->20% in some series. The survival differences may be related to stage, patient selection, and the expertise of the operative team. Preoperative chemotherapy/radiation is under study and may improve outcome. Clinical trial participation is essential for improvement in treatment outcomes.
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PMID:Pancreatic carcinoma in perspective. A continuing challenge. 868 Dec 96

In human pancreatic carcinoma (PCa) mutations in the p53 tumor suppressor gene are present in up to 50% of cases. Conformational change and cellular accumulation, together with subsequent release of mutant and normal p53 protein from transformed cells, may initiate a B-cell response with generation of circulating autoantibodies to p53 protein (anti-p53). In the present study we analyzed the sera of 85 consecutive patients with acute pancreatitis (N = 19), chronic pancreatitis (N = 33), and PCa (N = 33) to evaluate the specificity of autoantibodies to p53 protein as a serological marker for PCa. Detection of anti-p53 was performed using an enzyme-linked immunosorbent assay system with immobilized recombinant wild-type p53 protein. Autoantibodies to p53 were detectable in 1 of 19 patients with acute (5.3%) and in 4 of 33 patients with chronic pancreatitis (12.1%). All anti-p53-positive patients with acute or chronic pancreatitis were carefully examined and no underlying malignant disease was found. During follow-up (range, 281-647 days; mean, 472 days) none of these patients showed any evidence for subsequent development of PCa or any other malignant disease. In patients with PCa, anti-p53 was detected in 6 of 33 cases, resulting in a sensitivity of 18.2% with a specificity of 90.4%. In contrast to anti-p53, detection of serum carbohydrate antigen (CA 19-9) resulted in a sensitivity and specificity of 69.7 and 71.2% (CA 19-9, > 37 U/ml) and 51.5 and 96.2% (CA 19.9, > 100 U/ml) for the detection of PCa, respectively. Taken together, the sensitivity of anti-p53 formation was low in patients with PCa (18.2%). Furthermore, the detection of anti-p53 was not specific for malignancy, indicating that severe inflammatory processes may also induce anti-p53 formation.
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PMID:p53 autoantibodies in patients with pancreatitis and pancreatic carcinoma. 888 44

Genetic alterations such as K-ras mutation, inactivation of the p53, p16 and DPC4 genes and frequent chromosomal loss of the 17p, 9p, 18q and 1p are thought to play a crucial role in the carcinogenesis of pancreatic cancer. Mutations of K-ras oncogene could be detected frequently in pancreatic juice samples from patients with pancreatic carcinoma and intraductal papillary neoplasm (IPN), although they could be detected in some of the samples from patients with chronic pancreatitis and pancreatic cyst. This suggests that K-ras mutation is an early event in the carcinogenesis of the exocine pancreas. In IPN, analysis of other genetic alteration would be available, since pancreatic juice samples from the patient are relatively rich in the proportion of the tumor cells. A new diagnostic modality of sensitive allelotyping would be useful for evaluating malignant potential of these borderline lesions.
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PMID:[Molecular diagnosis of pancreatic cancer]. 927 65

Pancreatic cancer is the fifth leading cause of cancer death in the United States, and despite improvements in the results of surgical treatment for this disease, little impact has been made upon overall mortality. New advances in treatment will depend upon improved adjuvant therapy, early diagnosis, and a better understanding of tumor biology. This article summarizes the results of molecular genetic studies in pancreatic cancer and their potential clinical significance. Familial predisposition to pancreatic cancer, cytogenic studies, DNA ploidy analysis, and examination of specific oncogenes and tumor suppressor genes are reviewed. The most frequent mutations detected have been in the K-ras oncogene, which occur in 80% of pancreatic cancers. These mutations do not correlate with tumor stage or survival, but can be useful in differentiating pancreatic exocrine from endocrine tumors and chronic pancreatitis. Mutations in the p53 gene occur in approximately 50% of tumors, and appear to be an independent prognostic factor for patient survival. Mutations in the CDKN2 gene are frequently seen in sporadic pancreatic cancers, and have been implicated in cases of familial pancreatic cancer. The significance of mutations in APC, MCC, DCC, c-erbB-2, RB-1, and mismatch repair genes in the genesis of pancreatic cancer is less clear.
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PMID:The molecular genetics of pancreatic cancer. 936 57


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