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)

A cohort of patients with intraductal growth-type intrahepatic cholangiocarcinoma (IG-ICC) and its precursor lesions, collectively termed intraductal papillary neoplasm of the liver (IPNL), was characterized with respect to demographics, clinical manifestations, perioperative management, long-term survival, and molecular features associated with carcinogenesis. A total of 122 patients with IPNL types 1 through 4, 108 patients with non-IG-ICC and 210 patients with hepatolithiasis alone were studied. Expression of CDX2, TFF1, MUC1, MUC2, MUC5AC, EGFR, and p53 was determined by using immunohistochemistry. Females predominated in those with hepatolithiasis alone and IPNL. The mean age of patients with hepatolithiasis alone was 6 to 8 years younger than that of those with IPNL. The association with hepatolithiasis in patients with IPNL types 1 and 2, IPNL types 3 and 4, and non-IG-ICC was 100%, 79%, and 64%, respectively. Mucobilia, anemia, and elevated serum carcinoembryonic antigen levels were helpful in distinguishing IG-ICC and its precursor lesions. The mean survival of patients with IPNL type 3, IPNL type 4, and non-IG-ICC was 55.5 months, 36.9 months, and 15.8 months, respectively. The incidence of expression of CDX2 and TFF1 was maximal in IPNL type 3. Expression and cellular distribution of MUC2 and CDX2 were similar. MUC5AC was strongly expressed in all patients with IPNL; EGFR and p53 were rarely expressed in patients with IPNL. In conclusion, hepatolithiasis appears to be a precipitating factor in the development of IPNL. Signs of mucobilia were specific for the diagnosis of IPNL. Expression of CDX2 and MUC2 are helpful in differentiating IPNL and non-IG-ICC. Significant differences in survival associated with the various lesions studied warrants a more aggressive surgical strategy in their management.
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PMID:Characterization of intrahepatic cholangiocarcinoma of the intraductal growth-type and its precursor lesions. 1611 40

Epithelial neoplasms of appendix are infrequent, and their pathological features are not fully characterized. We collected 33 cases of appendiceal tumors and examined immunohistochemically the expression of cytokeratins (CK, CK7, and CK20), mucin core protein (MUC1, MUC2, MUC5AC, and MUC6), E-cadherin, chromogranin A, and p53 protein. Gene analysis of TP53 was also conducted on exons 5 to 8. Clinically, mucinous tumors were predominant in females. Immunohistochemically, all the tumors expressed CK20, whereas CK7 was positive in one third of the cases. Similarly, MUC2 was expressed in all the tumors, whereas MUC1 and MUC5AC were detected in about a half of the cases. Although chromogranin A-positive cells are generally sparse in normal appendix, they were more common in mucinous tumors than in nonmucinous tumors. Contrary to the previous data reported (Mod Pathol 2002;15:599-605), mucinous carcinoma exhibited a higher frequency of p53-positive cells (mean 29%) compared with mucinous adenoma (2.8%) (P < .001), whereas nonmucinous tumors showed high levels of p53-positive cells to similar extent (51%-67%) in both adenoma and carcinoma. The high expression of p53 protein coincided with the presence of mutations in multiple sites of TP53 gene in mucinous tumors. This is the first report that characterized the immunophenotypic profile of appendiceal epithelial neoplasms with an emphasis of a higher frequency of p53 positivity in mucinous carcinoma cases compared with mucinous adenoma in the appendix.
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PMID:Immunohistochemical expressions of cytokeratins, mucin core proteins, p53, and neuroendocrine cell markers in epithelial neoplasm of appendix. 1626 Feb 76

It has been suggested that right-sided and left-sided colorectal cancer may arise by different mechanisms. However, there have been few studies of mucinous adenocarcinoma (MA) in relation to location. Therefore, we analyzed clinicopathological characteristics, microsatellite instability (MSI), and expression of MUC1, MUC2, MUC5AC mucin core proteins, and p53 by immunohistochemistry in relation to tumor location. Ninety-six consecutive colorectal MAs and ninety-eight nonmucinous adenocarcinomas (nMAs) were investigated. Right-sided MAs, by comparison with those on the left side, were characterized by older age, larger tumor size, lower stage at presentation, peritumoral lymphocytic response, background of serrated adenoma, MSI-H phenotype, higher MUC2 and MUC5AC expression, and lower p53 protein overexpression. Right-sided nMAs, relative to those on the left side, were associated with MSI-H phenotype, higher MUC2 and MUC5AC expression, and lower p53 protein overexpression. Thus, MSI-H phenotype, expression of MUC2 and MUC5AC, and infrequent p53 protein overexpression are associated with right-sided location as well as mucinous histology. In univariate analysis, right-sided location had a favorable effect on disease specific survival of the patients with MA, although it is not an independent predictor of survival. Our results indicate that MA is a distinctive form of colorectal cancer and has different phenotypes depending on tumor location.
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PMID:Clinicopathological characteristics, microsatellite instability, and expression of mucin core proteins and p53 in colorectal mucinous adenocarcinomas in relation to location. 1664 63

A 44-year-old man was referred for a right chest nodule of 3 months duration. A 'benign' nodule had been excised from this location 8 years prior. On examination, palpable nodes were noted in the right axilla. Radiographic studies were significant only for right axillary lymphadenopathy. Histologically, a nodular dermal proliferation composed of poorly differentiated epithelioid cells in nests and focally forming ducts with pseudopapillary architecture comprised the primary tumor. Features of a clear cell hidradenoma were noted focally. Immunohistochemical (IHC) analysis revealed reactivity for HMW cytokeratins, CK5 and CK7, p53, p63, CEA (focal), androgen receptor, EGFR, estrogen receptor (ER), MUC5AC, and strong/diffuse membranous staining for Her-2/neu. Negative stains included villin, TTF-1, CDX2, S-100 protein, vimentin, gross cystic disease fluid protein 15 (GCDFP-15), mammoglobulin, and MUC2. A wide local excision and axillary node dissection was performed. Metastatic tumor involved nine of 28 nodes. Interphase fluorescence in situ hybridization (FISH) demonstrated chromosomal amplification of the Her-2/neu locus within the tumor and a nodal metastasis. The patient has completed adjuvant and radiotherapy, including trastuzumab, and is asymptomatic. We believe this to be the first demonstration of Her-2/neu amplification in a malignant skin adnexal tumor. In analogy to breast carcinoma, these findings suggest the applicability of trastuzumab for patients with metastatic adnexal carcinomas demonstrating Her-2/neu amplification.
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PMID:Metastatic hidradenocarcinoma with demonstration of Her-2/neu gene amplification by fluorescence in situ hybridization: potential treatment implications. 1721 55

Hepatoid adenocarcinoma is an extrahepatic tumor characterized by morphological similarities to hepatocellular carcinoma. The lesions contain a tubular adenocarcinoma that seems to develop "hepatoid" features, but the relation between the tubular adenocarcinomatous and the hepatoid components remains unclear. We compared the cellular phenotypes of 23 cases of hepatoid adenocarcinoma of the stomach having tubular adenocarcinomatous components with 69 cases of non-hepatoid adenocarcinoma of the stomach. Afterward, we examined the expression of CDX2 and p53 in the tubular adenocarcinomatous and hepatoid components of hepatoid adenocarcinoma. Both components of hepatoid adenocarcinoma were classified into 4 phenotypic categories according to the immunohistochemical results for CD10, MUC2, MUC5AC, and MUC6. The complete intestinal phenotype (CD10+, MUC5AC-, MUC6-) was most frequently observed in the adenocarcinomatous and hepatoid components (61% and 65%, respectively). In contrast, no gastric phenotype (MUC5AC+, MUC6+, MUC2-, CD10-) was observed in any of the hepatoid adenocarcinoma components. The positivity for p53 protein in the adenocarcinomatous and hepatoid components was concordant. The expression of CDX2 with early differentiation and maintenance of intestinal epithelial cells was observed in all of the adenocarcinomatous components, whereas 9 of the 23 hepatoid components (39%) were negative for CDX2. These findings suggest that hepatoid adenocarcinoma arises from an adenocarcinoma with an intestinal phenotype and that its hepatoid component is in some way related to reduced CDX2 expression.
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PMID:Hepatoid adenocarcinoma of the stomach: histogenesis and progression in association with intestinal phenotype. 1732 Jan 50

Pyloric-gland type adenoma of the gallbladder is formed by proliferation of glands resembling pyloric glands, morphologically. No previous report has described the cellular phenotype and differentiation of pyloric-gland type adenoma of the gallbladder, using CD10 as a marker of proper biliary phenotype. Immunostainings were performed for mucin markers such as MUC5AC, human gastric mucin (HGM) for gastric foveolar type epithelium, MUC6, M-GGMC-1 for pyloric-gland type and MUC2 for intestinal goblet-cell type, and for CD10 as a proper biliary type marker on 58 pyloric-gland type adenomas of the gallbladder, as well as for p53, Ki-67 and CDX2. The percentage (X) of reactive cells in relation to the total number of tumor cells was estimated semi-quantitatively, and divided into four categories: X=0% (negative), 0%<X<10%, 10%<or=X<30%, and X>or=30%. CDX2 expression was considered to be positive when the percentage of positively stained cells was >or=10%. Out of the 58 pyloric-gland type adenomas, >or=30% of adenoma cells were positive for MUC5AC in 22 (38%) tumors, HGM in 29 (50%), MUC6 in 58 (100%), M-GGMC-1 in 54 (93%), MUC2 in none (0%), and CD10 in 20 (34%). MUC6 (P<0.001) and M-GGMC-1 (P<0.001) mucins were detected more frequently in pyloric-gland type adenomas, and CD10 expression was significantly decreased, compared with normal gallbladder epithelium (P=0.006). P53 overexpression was not found in any of the 58 tumors, including two adenomas with carcinomatous foci. The mean number of Ki-67-positive cells was 10.3+/-5.8%. CDX2 expression was judged as negative in all 58 pyloric-gland type adenomas. In pyloric-gland type adenomas of the gallbladder, expression of pyloric-gland type mucins was observed with a high frequency, whereas intestinal goblet-cell mucins were rarely seen. In addition, co-expression of gastric foveolar type mucins and CD10 was also demonstrated. Pyloric-gland type adenomas of the gallbladder show a differentiation toward pyloric glands in terms of immunohistochemistry, as well as morphology, accompanied by co-expression of gastric foveolar and native biliary phenotypes.
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PMID:Co-expression of gastric and biliary phenotype in pyloric-gland type adenoma of the gallbladder: immunohistochemical analysis of mucin profile and CD10. 1734 6

Type 1 congenital cystic adenomatoid malformation (CCAM), the most frequent malformation of the lung, is the only type to present intracystic mucinous cell clusters, which may form beyond the cysts extracystic mucinous proliferation resembling mucinous bronchioloalveolar carcinomas (BACs). As mucinous BACs are increasingly described in the literature in young patients with CCAM, we hypothesized that type 1 CCAM mucinous cells could represent BAC precursors. We reviewed 7 cases of type 1 CCAM including 6 with intracystic mucinous cell clusters, 3 with extracystic mucinous proliferations, and 4 with mucinous BAC or mixed adenocarcinoma with predominant BAC. K-ras mutations at codon 12 were detected in 3/3 intracystic mucinous cell clusters, in 2/3 extracystic mucinous proliferations, and in 3/4 BAC. Loss of heterozygosity (LOH) at p16(INK4) locus, with microsatellite alterations in 3 cases, was observed in 2/3 intracystic mucinous cell clusters, in 2/3 extracystic mucinous proliferations, and in all BAC. Two extracystic mucinous proliferations showed LOH at FHIT and Rb loci, respectively. P16(INK4) expression was lost in 2 intracystic mucinous cell clusters, 1 extracystic mucinous proliferation, and 1 BAC. Neither epidermal growth factor receptor mutation on exons 18, 19, and 21 nor P53 accumulation was observed. All lesions expressed MUC5AC, but were negative for MUC2, CDX2, and TTF-1. In conclusion, type 1 CCAM mucinous cells share the same differentiation profile with corresponding mucinous BAC, consistent with a common bronchial origin. Moreover, the high frequency of K-ras mutation and LOH and/or microsatellite alterations at p16(INK4) locus presented by these mucinous cells justifies their consideration as BAC precursors.
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PMID:Mucinous cells in type 1 pulmonary congenital cystic adenomatoid malformation as mucinous bronchioloalveolar carcinoma precursors. 1752 88

Mucinous carcinoma of the colorectum is conventionally defined as carcinoma with an interstitial mucus component (MC) that occupies more than 50% of the tumor tissue. To examine the validity of this definition, we quantified the ratio between the area of MC and the total area of carcinoma (MC ratio) in 152 advanced colorectal carcinomas, and investigated whether MUC1, MUC2 and MUC5AC mucin expression, frequency of p53 overexpression, and peritumoral lymphocytic infiltration (PLI) of tumors differ in the MC ratio. Samples were classified into MC ratios of >50% (n=30), 10-50% (n=24), <10% (n=22), and 0% (n=76). Carcinomas with MC commonly possessed the MUC2+ phenotype (90.9-100%), and 76.6-83.3% possessed either the MUC2+/MUC5AC+/MUC1+ or the MUC2+/MUC5AC-/MUC1+ phenotype. Carcinoma without MC (MC ratio of 0%) was typically the MUC2- phenotype (89.5%). Frequencies of p53 overexpression of carcinomas with MC were significantly lower compared to those without MC (21-27% vs. 55%). PLI was observed in 0-4% of carcinomas with MC, but was observed in 17% of carcinomas without MC. These results indicate that colorectal carcinomas with MC can be grouped together as goblet cell type (MUC2+) carcinoma. These data also suggest that such carcinomas may have a common genetic background and alteration of immune responsiveness. Therefore, separately classifying carcinomas with an MC ratio of more than 50% as an independent histological type may be invalid, and re-evaluation of the histological classification of colorectal carcinoma may be required.
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PMID:Mucin expression, p53 overexpression, and peritumoral lymphocytic infiltration of advanced colorectal carcinoma with mucus component: is mucinous carcinoma a distinct histological entity? 1767 24

Presented herein is a rare case of invasive biliary cystic tumor without an ovarian-like stroma, and the apparent sequence underlying its malignant transformation, which was identified on detailed histological examination. A 54-year-old woman was incidentally diagnosed as having a cystic tumor in segment VIII of the liver, and central bisegmentectomy was performed. Macroscopically the tumor measured 4.6 x 3.5 cm; and unilocular cystic and solid areas were seen on cut surface. Microscopically the tumor showed three types of neoplasia: adenoma and tubulopapillary adenocarcinoma in the cystic area, and invasive adenocarcinoma in the solid area. The relative area of the tumor occupied by each of these histological types was approximately 3%, 50% and 47%, respectively. Moreover, transitional zones between adenoma and tubulopapillary adenocarcinoma, and between tubulopapillary adenocarcinoma and invasive adenocarcinoma were noted. The immunohistochemical expression of Ki-67 and p53 increased gradually from adenoma through to tubulopapillary adenocarcinoma, and was highest in invasive adenocarcinoma. MUC1 was positive, and MUC2 and MUC5AC were both negative. No ovarian-like stroma or communication with the bile ducts around the tumor was found in any area of the specimen. On the basis of the World Health Organization histological classification and these pathological findings, the present case was diagnosed as invasive-type biliary cystadenocarcinoma.
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PMID:Invasive biliary cystic tumor without ovarian-like stroma. 1798 81

We describe a rare case of esophageal polypoid dysplasia with gastric phenotype and focal intramucosal carcinoma associated with Barrett's esophagus. A 69-year-old man with a long history of gastroesophageal reflux disease was initially seen at an outside institution for evaluation of significant dysphagia. Screening upper gastrointestinal endoscopic evaluation revealed a large intraluminal polypoid lesion occluding the distal portion of the esophagus. Surgery was performed with resection of the distal esophagus and proximal stomach. The histopathologic examination of this lesion revealed an exuberant polypoid gastric epithelium with areas of low-grade dysplasia, high-grade dysplasia, and focal intramucosal carcinoma. A few residual foci of specialized intestinal metaplasia consistent with Barrett's esophagus without dysplasia were identified at the proximal and distal ends of the lesion. Immunohistochemically, this lesion revealed a pattern of expression of apomucins (MUC5AC diffusely positive, MUC1 and MUC6 focally positive, and MUC2 negative) consistent with a gastric foveolar phenotype. In addition, in the dysplastic areas, there was high Ki-67 labeling index and no overexpression of p53 protein. In our opinion, this case represents a precursor lesion of an extremely well-differentiated adenocarcinoma of gastric foveolar phenotype that has been previously documented in the stomach and in the duodenum and that now for the first time we report in the esophagus in association with Barrett's intestinal metaplasia.
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PMID:Esophageal polypoid dysplasia of gastric foveolar phenotype with focal intramucosal carcinoma associated with Barrett's esophagus. 1872 40


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