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)

Intraductal papillary-mucinous tumors (IPMTs) of the pancreas are characterized by dilated pancreatic ducts and ductules that are lined by tall columnar mucin-producing neoplastic epithelial cells. IPMTs have been suggested to be distinct neoplasms with a less aggressive phenotype than that of conventional ductal adenocarcinomas of the pancreas. Molecular mechanisms underlying tumorigenesis of IPMTs are beginning to be characterized. Allelic losses have frequently been detected at 9p, 17p, and 18q, suggesting that inactivation of tumor suppressor genes at these loci play a role in tumorigenesis of IPMTs. Using immunohistochemistry, we analyzed 38 IPMTs, including 9 hyperplasia, 16 adenoma, and 13 carcinoma tissues, for expression of p53, Ki-67, p16, and SMAD4. Nuclear p53 expression was observed in 5 (38%) of 13 carcinoma tissues but not in hyperplasia or adenoma tissues. Partial loss of p16 expression was observed in 9 (56%) and 12 (92%) of the 16 adenoma and 13 carcinoma tissues, respectively. Partial loss of p16 expression was observed even in adenomas with mild atypia. Partial loss of SMAD4 expression was observed in 6 (38%) and 12 (92%) of the 16 adenoma and 13 carcinoma tissues, respectively. The SMAD4 negative index was significantly higher in invasive carcinomas than in non-invasive carcinomas. Our results suggest that loss of p16 is an early event and p53 alteration is a late event during the progression of IPMTs. SMAD4 inactivation appears to be an early event but also involved in invasive tumor growth. Our results suggest that these alterations accumulate during the progression of IPMTs, reflecting results of analysis of allelic losses that showed a stepwise accumulation of genetic changes during progression.
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PMID:Differential roles of alterations of p53, p16, and SMAD4 expression in the progression of intraductal papillary-mucinous tumors of the pancreas. 1246 38

We report a localized malignant mesothelioma of the epithelial type, occurring as a primary hepatic neoplasm in a 64-year-old male. He was found to have a mass located in the right lobe of the liver. Surgery was carried out with resection of the mass from the right hepatic lobe, with partial resection of the diaphragm. Grossly, an ill-defined tumor was present in the hepatic parenchyma. Histologically, the tumor displayed a predominant tubular pattern of growth with a desmoplastic stroma. The tubules were lined by a single layer of cuboidal or flattened cells with pleomorphic vesicular nuclei. A hyaluronidase-digestible, mucin-like substance was demonstrated in the lumen and tumor cytoplasm. The tumor cells were immunohistochemically positive for calretinin, HBME-1, cytokeratin, i.e. AE1/AE3 and CAM 5.2, but negative for carcinoembryonic antigen, CD 34 and Leu M1. Moreover, the tumor cells showed nuclear accumulation of the p53 oncopotein and reacted frequently with Ki-67 antibody. These findings support the concept that malignant mesothelioma of the epithelial type may occur at extrapleural sites. To the best of our knowledge, this is the first reported case of localized malignant primary mesothelioma arising in the liver.
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PMID:Localized malignant mesothelioma of the epithelial type occurring as a primary hepatic neoplasm: a case report with review of the literature. 1258 19

p53 gene mutations play an important role in the pathogenesis of pancreatic carcinomas. Anti-p53 antibodies and p53 protein have been detected in the sera of patients with pancreatic carcinomas. However, very little is known about the clinical significance of these p53 antibodies. We investigated the relationship between anti-p53 antibodies and the presence of p53 protein in cancer cells and the serum, as well as other clinical factors. Anti-p53 antibodies were detected in 19 (23%) of 82 pancreatic-duct-cell carcinomas, and in one (5%) of 21 cases of chronic pancreatitis. However, no antibodies were detected in mucin-producing tumors or in islet-cell tumors of the pancreas. The anti-p53 antibodies were detected in both early and advanced stages. In those patients undergoing surgical resection for pancreatic duct-cell carcinomas, the prognosis of patients who were negative for the anti-p53 antibodies was better than patients who were positive. Of the 11 cases that were positive for anti-53 antibodies, 8 (73%) were also positive for the immunohistochemical expression of p53 protein in cancer cells. However, there was no significant correlation between the presence of anti-p53 antibodies and the serum p53 protein levels. These results suggest that the benefits of measuring the anti-p53 antibody titier as a screening test to detect pancreatic carcinoma are limited, but the presence of anti-p53 antibodies predicts a poor prognosis for postoperative pancreatic carcinoma patients.
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PMID:Clinical implication of anti-p53 antibodies and p53-protein in pancreatic disease. 1262 24

Our report describes a 66-yr-old man who underwent surgical resection of the pancreas twice within a period of 3 yr for primary and recurrent intraductal papillary mucinous tumors (IPMTs). During the second operation, a minute invasive ductal carcinoma (IDC) was accidentally discovered in the resected specimen of the residual pancreas. The similarity and continuity between this IDC and recurrent IPMT were not recognized histologically. A solid tumor was found in the hepatoduodenal ligament 3 mo after the second operation. We performed a third operation, performing laparotomy and intra-operative radiotherapy, but could not extirpate the tumor. A biopsy specimen obtained from the tumor during this third operation revealed adenocarcinoma, and the patient later died because of tumor progression. We immunohistochemically analyzed the expression of HER-2/neu, Smad4, p16, p21, p53, mucin immunophenotypes and the Ki-67 labeling index in this series of pancreatic-duct neoplasias. Overexpression of HER-2/neu and loss of Smad4 were detected in the minute IDC, which was very different from the immunohistochemical features of both the primary and recurrent IPMTs. The IDC also showed a MUC1-positive/MUC2-negative phenotype. Therefore, we suggest that de novo IDC may occur in IPMT patients, especially those with multiple tumor recurrence. The present case may be helpful in understanding the pathogenesis of pancreatic duct lesions.
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PMID:Minute invasive ductal carcinoma of the residual pancreas after distal pancreatectomy for intraductal papillary-mucinous tumor. 1262 31

We compared the histological and immunohistochemical features of mixed ductal-endocrine carcinomas of the pancreas with those of ductal adenocarcinomas (DACs) containing scattered tumor-associated endocrine cells (SECs). Three pancreatic neoplasms fulfilled the WHO criteria for mixed ductal-endocrine carcinomas. Two of them showed moderately to poorly differentiated glandular structures composed of both mucin producing and neuroendocrine cells. The third mixed ductal-endocrine carcinoma was of the composite type showing DAC structures and a solid component with small epithelial cells, most of them of neuroendocrine nature. In 32 of 34 cases of DAC located in the head (30 cases) and body to tail (4 cases) of the pancreas and showing lymph-node metastases, SECs were found, but they were few in number and irregularly distributed in the tumors. In three DACs a few SECs were also detected in lymph-node metastases. Double staining for chromogranin A and the proliferation marker Ki-S5 revealed that all SECs that were not intimately integrated into the neoplastic glandular epithelium failed to show proliferative activity and changes of the expression of tumor suppressor genes (p53 and DPC 4). These findings suggest that only those SECs that belong to the proliferative cell fraction may be of neoplastic origin, while the majority of SECs probably constitute a tumor-associated but non-neoplastic cell population. These features contrast with those of mixed ductal-endocrine carcinomas, in which all endocrine cells are a component of the neoplasm.
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PMID:Mixed ductal-endocrine carcinomas of the pancreas and ductal adenocarcinomas with scattered endocrine cells: characterization of the endocrine cells. 1264 16

There are a large number of stable pancreatic ductal carcinoma cell lines that are used by researchers worldwide. Detailed data about their differentiation status and growth features are, however, often lacking. We therefore attempted to classify commonly used pancreatic carcinoma cell lines according to defined cell biological criteria. Twelve pancreatic ductal adenocarcinoma cell lines were cultured as monolayers and spheroids and graded according to their ultrastructural features. The grading system was based on the integrity of membrane structures and on the presence of mucin granules, cell organelles, nuclear and cellular polymorphism, cell polarity, and lumen formation. On the basis of the resulting scores the cell lines were classified as well, moderately, or poorly differentiated. In addition, immunocytochemistry was performed for the markers cytokeratin 7, 8, 18, 19, carcinoembryonic antigen, MUC1 MUC2, MUC5, and MUC6. The population doubling time of monolayer cultures, determined by a tetrazolium salt based proliferation assay was correlated with the ultrastructural grade. The grading of the ultrastructural features of the monolayers, and particularly of the spheroids, revealed that Capan-1 and Capan-2 cells were well differentiated; Colo357, HPAF-2, Aspc-1, A818-4, BxPc3, and Panc89 cells were moderately differentiated and PancTu-I, Panc1, Pt45P1, and MiaPaCa-2 cells poorly differentiated. Membrane-bound MUC1 staining was a characteristic of well differentiated cell lines. The population doubling time of the monolayer cultures was related to the differentiation grade. No relationship was found between the p53, K-ras, DPC4/Smad4, or p16(INK4a) mutation status and the grade of differentiation. We conclude that the proposed ultrastructural grading system combined with the proliferative activity provides a basis for further comparative studies of pancreatic ductal adenocarcinoma cell lines.
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PMID:A comprehensive characterization of pancreatic ductal carcinoma cell lines: towards the establishment of an in vitro research platform. 1269 24

Although both sporadic colorectal cancer (CRC) and colitis-associated CRC arise from dysplastic precursor lesions and share several molecular alterations, the nature of the dysplasia and the frequency and timing of several of the key molecular changes differ enough to consider colitis-associated CRC a rather unique entity. To date, cancer surveillance in both ulcerative colitis and Crohn's colitis rests upon the detection of dysplasia. However, because there are considerable limitations to the detection and interpretation of dysplasia, there is a need for other molecular markers to complement the histologic analysis of dysplasia. Because patients with inflammatory bowel disease (IBD) undergo repeated, periodic surveillance colonoscopies, it affords an opportunity to study marker expression over time. Of the few markers that have been studied chronologically, aneuploidy, p53, and mucin-associated sialyl-Tn antigen expression each hold promise as markers of CRC risk in IBD. It will be important to study whether these markers, or other panels of gene or protein expression, can identify patients at highest risk for developing CRC in future clinical studies.
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PMID:Colon carcinogenesis in inflammatory bowel disease: applying molecular genetics to clinical practice. 1270 69

We report a case of biliary adenofibroma in a 47-year-old woman, who presented with right upper quadrant pain for several months. Abdominal imaging revealed a 16-cm solid and cystic mass in the left hepatic lobe. Histologically, the tumor showed two distinct components: 1) cystic and tubular structures lined by low columnar to cuboidal biliary-type epithelium, and 2) a dense fibrous stroma composed of spindle-shaped cells with only mild nuclear pleomorphism and inconspicuous nucleoli. Mitoses and stromal invasion were absent. The glandular epithelium stained positively for keratin AE.3/Cam 5.2, cytokeratin 7, cytokeratin 19, carcinoembryonic antigen, and epithelial membrane antigen and had a low Ki-67 proliferative index. In addition, the epithelium was positive for D10 but did not stain for 1F6 or acid mucin with alcian blue stain. This staining pattern, similar to bile duct hamartoma (von Meyenburg complex) with which this tumor shares morphologic similarity, suggests that biliary adenofibroma originates from interlobular or larger bile ducts. Three years after a subtotal resection no metastasis or significant tumor growth was noted. However, given the marked nuclear p53 immunoreactivity and tetraploidy status observed in this tumor, we cannot exclude that biliary adenofibroma may represent a premalignant process that warrants complete resection and thorough histopathologic examination.
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PMID:Biliary adenofibroma: a rare neoplasm of bile duct origin with an indolent behavior. 1271 55

Hepatoid adenocarcinoma of the stomach is a highly malignant neoplasm. Most gastric hepatoid adenocarcinomas coexist with tubular adenocarcinoma. However, the relationship between hepatoid adenocarcinoma and tubular adenocarcinoma is still unclear. In the present study, the characteristics of the coexistent tubular adenocarcinomas were determined by examining their profiles of mucin production. Subsequently, molecular pathological techniques were applied to determine the clonality of 15 mixed hepatoid and tubular adenocarcinomas of the stomach. Mucin analysis suggested that the coexistent tubular adenocarcinomas with hepatoid adenocarcinoma were of the intestinal type. The patterns of chromosome X inactivation were identical between the hepatoid adenocarcinoma component and tubular adenocarcinoma component in all of 3 informative female cases. Mutations in the p53 gene were found in 5 cases. The sequences were identical within both tumor components in all 5 cases. Microsatellite analysis indicated more than 3 common patterns of loss of heterozygosity in 8 cases. These observations strongly suggested that hepatoid adenocarcinomas were of identical origin to coexistent tubular adenocarcinomas.
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PMID:Histogenesis of hepatoid adenocarcinoma of the stomach: molecular evidence of identical origin with coexistent tubular adenocarcinoma. 1284 45

Hepatobiliary cystadenoma and cystadenocarcinoma of the gall bladder have rarely been reported. An 88-year-old Japanese man was admitted to our clinic because of hypochondralgia and jaundice. Imaging techniques revealed hemobilia and a multilocular cystic tumor in the fundus of the gall bladder, and cholecystectomy was performed. Grossly, the tumor (3.5 x 3 x 3 cm) was multicystic, containing seromucous fluid. The tumor was located in the fibromuscular layer and subserosa of the gall bladder fundus, and protruded into the serosal surface, not into gall bladder lumen. The mucosa appeared free of tumor involvement, and no gall stones were recognized. Microscopically, the tumor was located in the fibromuscular layer, subserosa and tiny focus of the mucosal surface. The tumor consisted of mucin-rich benign columnar cells, dysplastic mucous cells, malignant papillotubular cells and invasive carcinoma cells. Malignant and atypical tumor cells were located in the center of the tumor and in the tiny area of the mucosal surface, while benign tumor cells were located in the peripheral portions of the tumor and in the serosal side. Neither ovarian stroma-like mesenchymal stroma nor an oncocytic change in tumor cells was recognized. Non-tumorous gall bladder showed chronic cholecystitis. Immunohistochemically, benign and carcinoma cells were positive for cytokeratins, epithelial membrane antigen, CA19-9, MUC1, MUC5AC and MUC6, and carcinoma cells were also positive for carcinoembryonic antigen and p53 protein. The present case indicates that hepatobiliary cystadenocarcinoma without mesenchymal stroma may occur in the gall bladder of old men, and suggests that hepatobiliary cystadenoma without mesenchymal stroma may transform into hepatobiliary cystadenocarcinoma in the gall bladder.
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PMID:Hepatobiliary cystadenocarcinoma with cystadenoma elements of the gall bladder in an old man. 1462 5


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