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)

Immunohistochemical expression of the p53 protein was investigated in carcinoma of the gallbladder (n = 13), common bile duct (n = 7) and ampulla of Vater (n = 9) using the polyclonal, CM1, and monoclonal, DO7, antibodies (Novocastra). This was compared with cases of chronic cholecystitis (n = 11) and preneoplastic lesions of the gallbladder (n = 4) and ampulla (n = 3). Nuclear immunostaining for p53 protein was found only in the poorly differentiated adenocarcinomas of the gallbladder (n = 9) and were associated with a shorter patient survival period (median: 18.6 mths). The moderately differentiated adenocarcinomas (n = 4) did not show p53 immunostaining and were associated with a longer median survival period (26 mths). The gallbladder dysplasias and adenoma also had no p53 protein immunoreactivity. The common bile duct carcinomas did not stain for p53. Focal p53 immunoreactivity was present in only one (11%) of the cases of ampullary carcinoma and in one (9%) of chronic cholecystitis. In summary, increased p53 immunostaining was associated with reduced patient survival and found more frequently in poorly differentiated adenocarcinoma of the gallbladder but not in the better differentiated carcinoma, chronic cholecystitis or preneoplastic lesions of the gallbladder. The differences in p53 immunohistological expression between gallbladder, common bile duct and ampullary carcinomas justify further investigation into the molecular mechanisms responsible for their development.
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PMID:p53 protein immunoreactivity in cancers of the gallbladder, extrahepatic bile ducts and ampulla of Vater. 756 35

The expression of p53 protein was studied in formalin-fixed paraffin-embedded specimens of 41 well-differentiated adenocarcinomas of the gall-bladder, six cases of acute cholecystitis and 23 cases of chronic cholecystitis, using a monoclonal p53 (PAb 1801) antibody and streptavidin-biotin. p53 staining was divided into diffuse, focal or sporadic patterns. The relationship between the p53 Labeling Index (p53 LI) and cellular proliferation was also investigated using monoclonal Ki-67 (MIB1) antibody. Twenty-four of the 41 carcinomas (58.5%) had a diffuse staining pattern with a high p53 LI (47-93%) and 9.8% (4/41) had a focal staining pattern with an intermediate p53 LI (22-34%), with no relation to pT stage, tumor size, histologic type or grade of cytologic atypia. The p53 LI was higher than the Ki-67 LI in these tumors except for one. On the other hand, p53 staining was completely sporadic in the non-neoplastic specimens with a low p53 LI (0.2-2.8%). The p53-positive cells in these specimens were located only within areas of Ki-67-positive cells. In conclusion, p53-protein overexpression occurs as an early event in approximately 70% of well-differentiated adenocarcinomas of the gall-bladder, and this alteration is maintained during progression from intramucosal to invasive carcinoma. p53 immunostaining can distinguish malignant from benign lesions of the gall-bladder.
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PMID:p53 immunostaining distinguishes malignant from benign lesions of the gall-bladder. 770 45

In this study we investigated immunohistochemically the expression of p53 and c-erbB-2 proteins in 30 gall bladder adenocarcinomas, one carcinoma in situ, eight gall bladder epithelial dysplasias, and four cases of chronic cholecystitis. p53 expression could be found in 14 (47 per cent) adenocarcinomas and in two out of eight epithelial dysplasias. There were significantly more p53-positive grade II-III tumours than grade I tumours (P = 0.032 according to Fisher's exact probability test). c-erbB-2 expression was found in three (10 per cent) adenocarcinomas, but all dysplasias were c-erbB-2-negative. All three c-erbB-2-positive cases were also p53-positive. The results indicate that p53 mutations and c-erbB-2 gene alterations play a role in the neoplastic transformation of gall bladder epithelial cells. Co-expression of p53 and c-erbB-2 suggests that alterations of these genes might act in concert in the neoplastic transformation. The occurrence of p53 expression in gall bladder dysplasias suggests that p53 mutations could be an early event in the evolution of some gall bladder carcinomas, as has been suggested for some other types of tumours, such as lung squamous cell carcinomas.
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PMID:p53 and c-erbB-2 protein expression in adenocarcinomas and epithelial dysplasias of the gall bladder. 810 Aug 54

Gallbladder carcinoma is one of the most frequent neoplasms diagnosed in Chile. Although the premalignant lesions have been extensively studied and are well characterized, there is only limited information about the genetic abnormalities that might be important in the pathogenesis of gallbladder carcinoma or that might have prognostic implications. The present study evaluates the immunohistochemical expression of p53 protein in premalignant lesions and invasive carcinoma of the gallbladder, and correlates the p53 expression with histological type, grade of differentiation, and level of invasion of the tumor. The authors studied the immunohistochemical p53 protein overexpression in 52 gallbladder carcinomas, 47 carcinomas in situ (CISs), 34 dysplasias, and 10 specimens with chronic cholecystitis containing normal and metaplastic epithelium. A semiquantitative scoring system was used to assess the p53 reactivity. p53 overexpression was found in 34 of 52 (65.4%) carcinomas, 21 of 47 (44.7%) CISs, and 11 of 34 (32.4%) dysplasias. There were no significant differences in p53 expression in premalignant lesions associated with invasive carcinoma and those that were not. Normal and metaplastic epithelium did not overexpress p53 protein. In adenocarcinomas, no correlation was found between p53 protein overexpression and histological subtype, grade of differentiation, or level of invasion. The high incidence of p53 overexpression in gallbladder carcinoma and its presence in dysplasia, even in specimens without invasive carcinomas, suggests that this abnormality is an important and early event in the pathogenesis of the tumor. The progressively increasing incidence of p53 overexpression observed from premalignant lesions to invasive tumor provides additional support to the view that this is the usual route for the development of infiltrating gallbladder carcinoma.
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PMID:p53 protein overexpression in gallbladder carcinoma and its precursor lesions: an immunohistochemical study. 861 79

Ras oncogene mutation is found in many human malignancies. The ras family of genes consists of three functional genes which encode highly similar, guanine nucleotide-binding, proteins (p21) of 21kDa, with GTPase activity. The p21 protein is present on the inner aspect of the plasma membrane of a variety of cells. Using a polyclonal antibody, pan-ras p21 (Oncogene Science), the immunohistochemical expression of the ras oncogene in human gallbladder adenocarcinoma (n = 13) and dysplasia (n = 3), chronic cholecystitis (n = 11), common bile duct carcinoma (n = 6), together with ampullary carcinoma (n = 8) and carcinoma in situ (CIS) (n = 3), was examined. A statistically significant difference in ras p21 immunoreactivity between gallbladder cancers and chronic cholecystitis (P = 0.032; chi 2 test) was demonstrated. Strong ras p21 immunoreactivity was present in most gallbladder carcinomas (n = 8; 62%) but not in the cases of gallbladder dysplasia (n = 1; 33%) or chronic cholecystitis (n = 2; 18%). However, the ras p21 expression was strong in only a minority of the cases of ampullary carcinoma (n = 1; 13%), common bile duct carcinomas (n = 3; 50%), and none of the ampullary CIS, and was not shown to be statistically significant. There was no statistically significant correlation between ras p21 expression and patient survival (r = 0.18, r2 = 0.031, P = 0.56; simple regression analysis), or between ras p21 expression and p53 immunoreactivity (r = 0.13, r2 = 0.017, P = 0.47; simple regression analysis). In conclusion, ras p21 expression is increased in most cases of gallbladder carcinomas with no specific relationship to tumour grade suggesting that it may be important in the development of gallbladder carcinomas but not in its progression. No significant correlation was found between ras p21 expression and p53 immunoreactivity in gallbladder and biliary tract tumours and ras p21 immunoreactivity does not appear to be of any prognostic value. The lower rate of ras p21 overexpression in common bile duct and ampullary carcinomas suggests that these tumours may have a different molecular origin to gallbladder cancers.
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PMID:Ras p21 protein immunoreactivity and its relationship to p53 expression and prognosis in gallbladder and extrahepatic biliary carcinoma. 923 98

Carcinoma of the gallbladder has an unusual geographic and demographic distribution being more common in Israel, Bolivia, Chile and in Southwestern native Americans in the United States. Chronic cholecystitis, choledochal cysts and significantly high body mass index are associated risk factors. Over 90% of gallbladder carcinomas are adenocarcinomas. Advanced local and regional disease usually is present at the time of diagnosis. P53 protein overexpression and p53 mutation may be related to increasing grade of cytologic atypia and to invasiveness. K-ras gene mutation occurs in both dysplasia and carcinomas. Ultrasonography, CT, MRI are diagnostic measures that can provide accurate staging information. Overall, the curative resection rates for gallbladder carcinoma range from 10% to 30%. During laparoscopic cholecystectomy, gallbladder cancer may be inadvertently discovered necessitating a more extensive resection. For those with unresectable disease, palliative surgical, endoscopic or radiologic bypass procedures can improve quality of life. Other approaches to the management of advanced tumors include combined radiation and chemotherapy and systemic chemotherapy.
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PMID:Gallbladder carcinoma. 1043 4

Gallbladder carcinoma is an uncommon but highly malignant tumor with a poor 5-year survival rate. The presence of gallstones is a well-established risk factor for gallbladder carcinoma, and the risk seems to correlate with stone size. Metaplastic changes of the gallbladder epithelium present in chronic cholecystitis may be a premalignant lesion. Solitary polyps with a size of greater than 1 cm are recognized as a predisposing factor for gallbladder carcinoma when their characteristics are echopenic, sessile, and high cell density. Endoscopic ultrasound is the most useful technique to detect the early changes of malignancy in polyps. Anomalous junction of pancreaticobiliary ducts (AJPBD) without a choledochal cyst and porcelain gallbladder is an additional risk factor for gallbladder malignancy. At the molecular level, it has been proposed that chronic inflammation of the gallbladder may lead to the loss of p53 gene heterozygosity and excessive expression of p53 protein. Furthermore, a proposed mechanism underlying the high risk of gallbladder carcinoma in patients with AJPBD is that chronic reflux of pancreatic juice causes intestinal metaplasia, hyperplasia, and dysplasia with the mutation of p53 and K-ras. In contrast, the causal relationship between porcelain gallbladder and malignancy is yet to be established. In this article, recognition of risk factors for gallbladder carcinoma was summarized with special attention to gallstones and chronic inflammation.
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PMID:Carcinogenesis of malignant lesions of the gall bladder. The impact of chronic inflammation and gallstones. 1138 26

A precancerous change has been identified incidentally in resected specimens from patients who have undergone cholecystectomy. We focused on chronic cholecystitis, showing a thick and sclerotic wall caused by recurrent inflammation, e.g. contracted cholecystitis, and examined the malignant potential of these lesions. We studied 88 patients who had undergone cholecystectomy. Contracted cholecystitis was diagnosed, using our criteria, in 28 of these cases. Ordinary chronic cholecystitis was diagnosed in 50 cases and gallbladder carcinoma in ten cases. We examined the expression of p53, Ki-67, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) immunohistochemically. Severe dysplasia or carcinoma in situ in a very small portion of the specimen was identified with hematoxylin-eosin staining in four cases (14.3%) of contracted cholecystitis. These specimens revealed a positive expression of not only p53, but also Ki-67, iNOS, and COX-2. Statistical significance was shown among the three disease groups in terms of the incidence of p53 overexpression, respectively (P<0.05). The results of this study suggest that contracted cholecystitis could be an early change leading to carcinogenesis.
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PMID:Significance of contracted cholecystitis lesions as high risk for gallbladder carcinogenesis. 1141 Mar 19

Xanthogranulomatous Cholecystitis is a chronic inflammatory disease of the gallbladder, a variant of the chronic cholecystitis. As xanthogranulomatous cholecystitis is occasionally seen with carcinoma of the gallbladder, the association with cancer is a controversial issue. A focal type of xanthogranulomatous cholecystitis is found simultaneously with gastric cancer diagnosed preoperatively. The resected specimen was genetically studied. Polymerase chain reaction amplification, single-strand conformational polymorphism analysis for mutation of p53 showed no abnormality indicating that less association with cancer in which the mutation of p53 is often seen. Etiopathologic factors of xanthogranulomatous cholecystitis might have relation with cancer, but xanthogranulomatous cholecystitis itself may not be the direct cause for cancer.
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PMID:Genetic analysis of xanthogranulomatous cholecystitis: precancerous lesion of gallbladder cancer? 1214 46

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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