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 performed a retrospective analysis of potential prognostic markers in 260 patients with surgically resected stage I and II non small-cell lung cancer (NSCLC) with a minimum 5-year follow-up. Cox proportional hazard models and Wilcoxon tests were employed to analyze the effect of patient characteristics on survival and disease-free survival (DFS). In the univariate analysis, the following were significant predictors of shorter overall survival: N-stage (N1 vs N0) (p<0.001); T-stage (T2 vs T1) (p<0.001); antigen A (loss vs presence) (p<0.01); cough (present vs absent) (p=0.01); bcl-2 expression (positive vs negative) (p=0.03); age (>63.5 vs <63.5) (p=0.03); mucin (positive vs negative) (p<0.03). The following were significant predictors of shorter DFS: N-stage (p<0.001); T-stage (p=0.001); loss of antigen A (p=0.01); mucin expression (p<0.01); cough (p=0.02); Ki-67 expression (p=0.02) and negative bcl-2 expression (p=0.03). Analysis of survival difference for histologic subtype, degree of differentiation, aneuploidy, %S-phase, codon 12 K-ras mutation, and immunohistochemistry staining for Lewisy, p53, Rb, microvessel count, HER2, E-cadherin and neuroendocrine markers did not reach statistical significance. In multivariate analysis, the following predicted for shorter overall survival: N-stage (p<0.01), antigen A (p=0.01), age (p<0.01), and bcl-2 (p=0.05); and for DFS, N-stage (p<0.01), antigen A (p<0.01), Ki-67 (p=0.03), mucin (p=0.04) and T-stage (p=0.05). Of all the clinical-pathological, proliferative, and biological markers studied, only a few carried independent prognostic significance.
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PMID:Prognostic markers in resected stage I and II non small-cell lung cancer: an analysis of 260 patients with 5 year follow-up. 1472 52

Three cases of a distinctive intraductal tubular adenoma, pyloric type, of the main pancreatic duct are reported. The patients, two women and a man, whose ages ranged from 63 to 70 years, complained of abdominal pain attributed to chronic pancreatitis in two patients. The patient with the largest tumor also had symptoms of gastric outlet obstruction. The tumors, two of which arose in the head and one in the tail of the pancreas, led to occlusion and cystic dilatation of the main pancreatic duct. Two adenomas were sessile and one was attached to the wall of the pancreatic duct by a thin fibrous stalk. Microscopically, they were composed of lobules of closely packed tubular glands similar to pyloric glands. In one tumor, nearly all glands were lined by columnar mucin-secreting cells with abundant clear cytoplasm and basally oriented nuclei. In addition to pyloric glands, two adenomas contained glands lined by cells with little or no mucin as well as by pink oncocytic cells. Focal intestinal differentiation was identified in one tumor. Both intracellular and extracellular mucin was detected with the mucicarmine, periodic acid-Schiff, and alcian blue stains. All three adenomas were CK7 positive and CK20 negative. Focal carcinoembryonic antigen linear reactivity along the apical cytoplasm was seen in many cells, but few cells expressed cytoplasmic carcinoembryonic antigen. All three adenomas showed low proliferative activity as measured by the MIB-1 labeling index. The three adenomas were p53 negative and showed loss of DPC4 expression. No endocrine cells were identified in any of the tumors. All patients are alive and symptom free from 4 months to 5 years following surgical treatment.
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PMID:Intraductal tubular adenoma, pyloric type, of the pancreas: additional observations on a new type of pancreatic neoplasm. 1504 13

In rats, esophagogastroduodenal anastomosis (EGDA) without concomitant chemical carcinogen treatment can lead to columnar-lined esophagus (CLE) including metaplasia, dysplasia, and esophageal adenocarcinoma (EAC). This study describes the morphology and phenotypic features of CLE and EAC in the rat model and compares them with the corresponding lesions in human Barrett's esophagus (BE). Swiss roll preparations of esophagi of EGDA rats and biopsies from human BE containing specialized intestinal metaplasia (SIM) and EAC were examined. The esophagi of EGDA rats showed esophagitis, CLE, islands of multilayered epithelium (MLE), dysplasia and EAC. The CLE had features of specialized intestinal metaplasia. MLE frequently occurred at the neo-squamocolumnar junction and occasionally in the mid-esophagus in isolated foci. Scattered mucinous cells in esophageal squamous epithelium were also found. The CLE and MLE in EGDA rats resembled the lesions described in human BE in morphology, mucin features and expression of differentiation markers (CK7, CK20, Das-1, villin, and pS2/TFF1). Invasive EAC in EGDA rat is of well-differentiated mucinous type, which is in contrast to the variably differentiated glandular type of adenocarcinoma in human BE. p53, c-myc, and cyclooxygenase 2 are expressed in both the rat and human SIM and EAC. These studies indicate that, not withstanding small differences, SIM and EAC induced in EGDA rats are similar to the corresponding lesions in human BE. EGDA rats may serve as a useful model to study the pathogenesis, molecular biology, and chemopreventive interventions of human BE and EAC.
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PMID:Phenotype of columnar-lined esophagus in rats with esophagogastroduodenal anastomosis: similarity to human Barrett's esophagus. 1509 11

There are differing views between Western and Japanese pathologists on the use of histological criteria to classify gastrointestinal tumors. It is therefore a priority to create a new histological classification of the stomach in order to resolve the confusion. Expression patterns were examined of mucin (MUC2, CD10, MUC5AC, pyloric gland-type mucin), p53 protein, and Ki-67 in tumor cells according to the following new classification system for differentiated-type intramucosal neoplastic lesions of the stomach, based on nuclear atypia: borderline neoplasia (adenoma (including dysplasia), indefinite tumor of adenoma or low-grade cancer, and low-grade cancer) and definite carcinoma (intermediate cancer, and high-grade cancer). The resulting grades were: adenoma, 23; indefinite tumor for adenoma or low-grade cancer, 6; low-grade cancer, 28; intermediate cancer, 48; high-grade cancer, 20. While the frequency of intestinal-type borderline neoplasias was higher than that of definite carcinomas, the mixed-type of definite carcinomas occurred with higher frequency than borderline neoplasias. The p53 protein overexpression and the Ki-67-positive rate increased with an increase in the grade assigned according to the new classification. The correlated expression levels of p53 protein, Ki-67, and various mucins, support the conclusion that this classification of intramucosal neoplastic lesions is useful for obtaining a consensus diagnosis of gastric intramucosal neoplasia between pathologists and gastrointestinal clinicians.
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PMID:Analysis of mucin, p53 protein and Ki-67 expressions in gastric differentiated-type intramucosal neoplastic lesions obtained from endoscopic mucosal resection samples: a proposal for a new classification of intramucosal neoplastic lesions based on nuclear atypia. 1514 2

We examined the expression of MUC1, MUC2, MUC5AC, and MUC6 by immunohistochemical staining in atypical adenomatous hyperplasia (AAH), bronchioloalveolar carcinoma (BAC), and adenocarcinoma with mixed subtypes (MX) to study the association between the biologic features of adenocarcinoma of the lung and mucin expression. MUC1 expression was decreased significantly in the progression from AAH through BAC to MX, while the levels of expression of MUC2, MUC5AC, MUC6, and depolarized MUC1 were increased significantly. Alterations in the expression of depolarized MUC1, MUC5AC, and MUC6 were correlated significantly with p53 gene abnormalities. Depolarized MUC1 expression also was correlated significantly with Ki-67 expression, and down-regulation of MUC1 expression and up-regulation of MUC6 expression were correlated significantly with tumor size. Our results suggest that the expression of these mucins might be associated with the progression of adenocarcinoma of the lung.
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PMID:Expression of MUC1, MUC2, MUC5AC, and MUC6 in atypical adenomatous hyperplasia, bronchioloalveolar carcinoma, adenocarcinoma with mixed subtypes, and mucinous bronchioloalveolar carcinoma of the lung. 1515 Dec 4

Recent molecular studies have shown that the genetic profiles of differentiated-type adenocarcinomas of the stomach are associated with distinct cellular mucin phenotypes (gastric- intestinal- and mixed-phenotypes). Therefore, we examined whether these cellular mucin phenotypes reflect specific molecular genetic alterations, and whether the phenotypes can be used to help categorize the intramucosal neoplasias of gastric tumors. We subclassified tumors into four cellular phenotypes using immunohistochemical mucin analysis. In all, 62 early gastric carcinomas (gastric-phenotype, 13; intestinal-phenotype, 17; mixed-phenotype, 31; unclassified-phenotype, 1) were examined using a combination of polymerase chain reaction microsatellite assays and immunohistochemical analysis in order to detect chromosomal allelic losses of multiple cancer-related chromosomal loci (1p, 3p. 4p, 5q, 8p, 9p, 13p, 17p, 18q and 22q), microsatellite instability (MSI), and overexpression of the p53 protein. In addition, we analyzed the relationship between MSI status and hMLH1 promoter hypermethylation, which is thought to be a cause of high MSI status. For gastric phenotype cancers, the frequency of 3p allelic loss was higher than that of other microsatellite markers, whereas 5q allelic loss was frequently found in intestinal phenotype cancers. The genetic profile of mixed phenotype cancers is comprised of two distinct genetic types: LOH and MSI types. In the former, 5q, 3p and 18q allelic losses are seen frequently in intramucosal carcinomas. On the other hand, 17p, 1p and 9p allelic losses are associated with the development of submucosal carcinomas. MSI was observed only in mixed phenotype cancers (six of 31 mixed phenotype cancers). Overexpression of the p53 protein is common in differentiated-type gastric cancers. In addition, the MSI status of the tumor cells was correlated with the extent of hypermethylation of the hMLH1 promoter. We suggest that the cellular mucin phenotypes of the differentiated-type adenocarcinomas result from distinct genetic alterations.
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PMID:Three independent genetic profiles based on mucin expression in early differentiated-type gastric cancers--a new concept of genetic carcinogenesis of early differentiated-type adenocarcinomas. 1515 9

We present a unique carcinoma of the pancreas with predominantly clear cell morphology (>95% clear cells). Mucicarmine stain revealed abundant intraluminal and intracytoplasmic mucin. Immunohistochemically, the cells were positive for the epithelial markers cytokeratin 7 and CAM 5.2, and were focally positive for cytokeratin 20. These cells also expressed monoclonal carcinoembryonic antigen. Stains for the neuroendocrine markers synaptophysin and chromogranin were negative, as were stains for vimentin, p53, HMB-45, and CD10. An additional outstanding feature was the presence of dense intraluminal and intracytoplasmic hyaline globules, which were immunohistochemically positive for alpha1-antitrypsin. Sequencing of the K-ras oncogene revealed a point mutation in codon 12, providing molecular evidence of ductal origin. In the proper morphologic context supported by immunohistochemistry, clear cell carcinoma can be regarded as a rare variant of ductal adenocarcinoma.
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PMID:Clear cell ductal adenocarcinoma of pancreas: a case report and review of the literature. 1516 26

Both the availability of multiple treatment modalities and novel therapeutic targets make the correct prognostic stratification and the identification of truly predictive factors an issue of major debate in gastric cancer. Along with "classic" prognostic factors such as those related to the diffusion of the tumour at diagnosis (i.e., depth of gastric wall infiltration, locoregional lymph nodes or distant metastases) or those concerning the pathologic characteristics of the tumour, other, innovative, factors should be considered if a better definition of the characteristics of the tumour is to be given. These biological factors are often derived from the genetic process, which is thought to represent a crucial step to gastric cancer (DNA copy number changes, microsatellite instability, thymidilate synthase, E-cadherin, beta-catenin, mucin antigen, p53, c-erb B-2, COX-2, matrix metalloproteinases, VEGFR and EGFR). Some of those putative prognostic indicators can also be considered predictive of response to therapy as they are a molecular target either to chemotherapeutics (i.e., thymidilate synthase that is targeted by 5FU) or to a new class of antineoplastic molecules (i.e., c-erb B-2 targeted by trastuzumab, COX-2 by NSAIDs, matrix metalloproteinases, EGFR and VEGFR by specific inhibitors).
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PMID:Molecular biology of sporadic gastric cancer: prognostic indicators and novel therapeutic approaches. 1524 77

The scope of this work was to determine the potential use of prostatic conventional histologic parameters and biologic factors in distinguishing between paramalignant and malignant prostatic disease, taking into account benign fragments of biopsies obtained from patients with prostatic cancer or from patients suspected to have cancer. Each prostate sample was semi-quantified for macronucleoli, mucin, crystalloid, collagen micronodules, and quantified for glands, stroma, AgNOR, and p53. The database covered 185 biopsy specimens from 136 patients: 56 samples from the same number of patients in whom all the biopsies were benign; 49 samples from patients whose biopsies showed malignant features, and 80 malignant samples. Discriminant analysis of the results showed statistical differences for four parameters: macronucleoli, mucin, gland volume, and AgNOR, allowing us to identify three patterns of prostate involvement: normal, paramalignant, and malignant. The discriminant function permitted an adequate classification of the three patterns in 84% of the cases. Normal areas showed glands with a mean volume of 38.93 microm3, inconspicuous nucleoli, low mucin production, and a mean AgNOR area of 1.26 microm2. Prostatic biopsies with prominent nucleoli and the presence of mucin (60%), gland volume of 22.31 microm3, and AgNOR area of 2.14 microm2 characterized the paramalignant condition. Malignant areas were characterized by mean glands with a volume of 8.11 microm3, prominent nucleoli, high mucin secretion (100%), and AgNOR area of 4.47 microm2. We concluded that modifications in prostate histoarquitecture and function, such as the presence of macronucleoli, volume of glands, abnormal secretion of acid mucin and AgNOR expression, represent important parameters that must be incorporated in the pathologist's evaluation of prostate biopsies to the purpose of indicating a subsequent biopsy, particulary in those patients with clinical suspicion of malignancy, and whose prostate biopsy specimen showed paramalignant areas.
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PMID:Quantitation of conventional histologic parameters and biologic factors in prostatic needle biopsy are useful to distinguish paramalignant from malignant disease. 1549 72

Pancreatic mucinous cystic tumors (MCT) are proliferations of mucin-producing epithelia supported by an ovarian-like stroma. They are classified into adenomas (MCA), borderline (MCB) and noninvasive or invasive carcinomas (MCC). The molecular mechanisms underlying their clinical behavior are poorly understood, partly due to the lack of cellular models. We report the establishment of MCC1, the first cell line from a pancreatic MCT, deriving from the highly dysplastic cell component of a noninvasive MCC. MCC1 has mutations in codon 12 of K-RAS (GGT>GAT), codon 58 of P16 (CGA>TGA) and codon 132 of P53 (AAG>AGG). The FHIT and DPC4 genes are unaltered. Immunohistochemistry shows abnormal expression of MUC1 and p53, loss of p16 and retention of Fhit and Dpc4 in both the cell line and the highly dysplastic cells of the primary lesion. The morphological and molecular features of MCC1 and its corresponding primary tumor are consistent with a model for non-invasive MCC, where K-RAS, P16, P53 and MUC1 alterations are pre-invasive changes associated with progression of malignancy of MCT from adenoma to carcinoma. MCC1 is sensitive to 5-fluorouracil, representing the first assessment of drug sensitivity for MCC. Finally, MCC1 is a suitable model for preclinical studies, as it grows in immunodeficient mice.
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PMID:Mucinous cystic carcinoma of the pancreas: a unique cell line and xenograft model of a preinvasive lesion. 1568 69


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