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 report a cribriform carcinoma of the left fossa poplitea in a 62-year-old woman. The patient did not present any symptoms, and the only complaint was the nodule, which was resected for diagnosis. After considering different diagnostic options, we decided that the most appropriate one was cribriform carcinoma, which is an entity described in 1998. The diagnostic criteria, which were provided in the few publications that refer to this entity, helped us to distinguish it from the main mimicker: cystic adenoid carcinoma. Owing to the cribriform pattern of the tumor, we also looked for a metastasis from other sites, mainly breast, vulva, and salivary glands, but all these were clinically excluded. The tumoral cells showed secretion by decapitation, as well as a positive stain of the luminal secretion by histochemical techniques of Alcian blue and periodic acid-Schiff. The tumor was negative for iron stain. In spite of these characteristics, which are, for some authors, indicative of an apocrine phenotype, the immunohistochemical study revealed some differences with the profile that has been described in cases of apocrine adenocarcinoma. The tumor did not express GCDFP-15 or CD 15. It was also negative for SMA, CEA, and PR. The pattern of cytokeratins expressed by our case was positive for AE1-AE3, CAM 5.2, and CK7, without any expression for CK20. Other markers expressed by the tumor were EMA, ER, c-erbB-2, p53, and S-100.
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PMID:Immunohistochemical phenotype of cutaneous cribriform carcinoma with a panel of 15 antibodies. 1808 81

PR-Set7/SET8 is a histone H4-lysine 20 methyltransferase required for normal cell proliferation. However, the exact functions of this enzyme remain to be determined. In this study, we show that human PR-Set7 functions during S phase to regulate cellular proliferation. PR-Set7 associates with replication foci and maintains the bulk of H4-K20 mono- and trimethylation. Consistent with a function in chromosome dynamics during S phase, inhibition of PR-Set7 methyltransferase activity by small hairpin RNA causes a replicative stress characterized by alterations in replication fork velocity and origin firing. This stress is accompanied by massive induction of DNA strand breaks followed by a robust DNA damage response. The DNA damage response includes the activation of ataxia telangiectasia mutated and ataxia telangiectasia related kinase-mediated pathways, which, in turn, leads to p53-mediated growth arrest to avoid aberrant chromosome behavior after improper DNA replication. Collectively, these data indicate that PR-Set7-dependent lysine methylation during S phase is an essential posttranslational mechanism that ensures genome replication and stability.
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PMID:PR-Set7-dependent lysine methylation ensures genome replication and stability through S phase. 1815 31

We obtained 22 sessile serrated adenomas (SSAs) and 19 hyperplastic polyps (HPs) and performed immunolabeling for cytokeratins (CKs) 7 and 20, CDX2, beta-catenin, and p53 to determine the role of these markers in aiding distinction of lesions with neoplastic potential. Patients with SSAs more frequently had a prior or coexistent tubular adenoma (P = .004) that was right-sided (P = .00001) and larger (P = .03). No difference in CK7, CK20, or p53 labeling was found after correction for colonic location. However, CDX2 labeling was significantly lower in SSAs (P = .02) and was predominantly confined to the crypt bases, whereas it was diffusely positive in HPs (P < .001). Surprisingly, aberrant nuclear labeling for beta-catenin was found in 9 (41%) of the SSAs but in none of the HPs (P < .002). We propose that beta-catenin and/or CDX2 immunolabeling may have diagnostic usefulness in the evaluation of serrated polyps. These findings also suggest that Wnt signaling has a role in SSA development.
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PMID:Frequent beta-catenin nuclear labeling in sessile serrated polyps of the colorectum with neoplastic potential. 1828 64

Papillary urothelial neoplasms with deceptively bland cytology cannot be easily classified. We aimed to design a new algorithm that could differentiate between these neoplasms based on a scoring system. We proposed a new scoring system that enables to reproducibly diagnose non-invasive papillary urothelial tumors. In this system, each lesion was given individual scores from 0 to 3 for mitosis and cellular thickness, from 0 to 2 for cellular atypia, and an additional score for papillary fusion. These scores were combined to form a summed score allowing the tumors to be ranked as follows: 0-1 = UP, 2-4 = low malignant potential (LMP), 5-7 = low-grade transitional cell carcinoma (TCC), and 8-9 = high-grade TCC. In addition to the scoring system, ancillary studies of MIB and p53 indexes with CK20 expression pattern analyses were compared together with clinical parameters. The MIB index was strongly correlated with disease progression. Four of the 22 LMP patients (18.2%) had late recurrences, two of these four (9.1%) had progression to low-grade carcinoma. The MIB index for LMP patients was strongly associated with recurrence (recurrence vs. non-recurrence, 16.5 vs. 8.1, p < 0.001). The proposed scoring system could enhance the reproducibility to distinguish papillary urothelial neoplasms.
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PMID:Diagnostic algorithm for papillary urothelial tumors in the urinary bladder. 1831 91

We present a 6-year-old child with intraocular and extraocular mass and high intraocular pressure. The tumor mass involved a disorganized anterior segment and extended through the medial cornea and sclera. A preliminary diagnosis of retinoblastoma with extraocular extension was made. An exenteration of the left globe and orbital tissue was performed. Histological examination showed that the lesion, which occupied the posterior chamber, involved the ciliary body, extending into the iris, sclera and cornea, projecting beyond the cornea anteriorly and extending to the retina posteriorly. The tumor cells were diffusely immunoreactive to vimentin, neuron specific enolase and CD 138. The medulloepithelioma cells were focally positive to cytokeratin (AE1/AE3), cytokeratin 18, CD56,CD57, S100, HMB-45 and bcl2 while areas of retinoblastic differentiation showed diffuse immunoreactivity to synaptophysin, neurofilament and CD138 with focal immunoreactivity to calretinin. All tumor cells showed no immunoreactivity to cytokeratin 7, cytokeratin 20, epithelial membrane antigen, carcinoembryonic antigen, desmin, GFAP, and chromogranin. Nuclear staining for P53 was seen in 80% of tumor cells. The ki-67 index was 90%. The tumor was described as malignant intraocular non-teratoid medulloepithelioma with retinoblastic differentiation arising from the ciliary body. Tumor satellites were seen in the adjacent periocular soft tissue. The treatment involved exenteration of the left globe and orbital tissue with secondary skin graft following chemotherapy. The patient is well and has no recurrence after 1 year of treatment. We report that medulloepithelioma can present as a case of infantile glaucoma, can show signs of intraocular calcifications and can show retinoblastic differentiation.
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PMID:Malignant non-teratoid medulloepithelioma of ciliary body with retinoblastic differentiation: a case report and review of literature. 1841 Feb 70

Pagetoid spread of primary esophageal melanomas and several cases of pagetoid esophageal squamous cell carcinoma are known. However, true esophageal Paget disease (intraepithelial growth of neoplastic cells with glandular differentiation) has only rarely been reported. We encountered 3 endoscopic biopsy specimens containing Paget cells in squamous epithelium associated with adenocarcinomas in Barrett esophagus (BE) and in the esophagogastric junction. To determine the prevalence of Paget cells in the esophagus, we studied 81 endoscopic mucosal resections and 27 esophagectomies from patients with invasive or intramucosal adenocarcinoma, and compared the findings to a control group of 47 endoscopic mucosal resections and 25 esophagectomies from patients with high-grade dysplasia in BE. Paget cells were present in squamous epithelium overlying 5 (4.9%) of 108 adenocarcinomas but in none (0%) of 72 BE with high-grade dysplasia (P=0.16). A computerized search for primary Paget disease using the terms "Paget's and esophagus" or "pagetoid and esophagus" from 1994 to 2007 did not yield any additional cases. Among the 8 patients with Paget cells (including the 2 index biopsies) there were no differences in either sex distribution (7M:1F) or age (mean 62.4 y) as compared with 103 adenocarcinomas without Paget cells (93M:10F, P=0.58; mean age 69.2 y, P=0.78). Morphologically, all adenocarcinomas with Paget cells contained at least a component of diffuse, poorly differentiated adenocarcinoma, and 1 was a signet ring cell carcinoma. Paget cells involved only squamous epithelium directly above the poorly differentiated tumor foci. Histochemistry for periodic acid-Schiff with diastase (PAS-D) and mucicarmine, and immunohistochemistry for CK7, CK20, p53, and E-cadherin, were performed on 7 Paget cases with the following results: PAS-D+ (7 of 7, 100%), mucicarmine+ (6 of 7, 86%), CK7+ (7 of 7, 100%), CK20+ (5 of 7, 71%), p53 overexpression (3 of 7, 43%), and E-cadherin loss (complete loss in 1 and faint expression in 3, 57%). Overall, PAS-D was the most efficacious stain for highlighting Paget cells. A control group of 19 adenocarcinomas without Paget cells were also stained for E-cadherin; only 1 showed faint expression (5%) and none showed complete loss (P=0.01). These results demonstrate a low but significant prevalence (4.9%) of Paget cells in esophageal and esophagogastric junction adenocarcinomas. Unlike previously described cases of mammary, vulvar, and perianal Paget disease, esophageal Paget cells are almost universally associated with underlying adenocarcinoma and not with high grade dysplasia ("in situ" disease) or primary Paget disease. A commonality among cases with Paget cells is the presence of focal or diffuse, poorly differentiated adenocarcinoma with discohesive cells. E-cadherin alterations seem to play a less significant role.
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PMID:Paget cells in the esophagus: assessment of their histopathologic features and near-universal association with underlying esophageal adenocarcinoma. 1849 41

Molecular dynamics simulations employing a molecular mechanics (MM) force field and hybrid quantum mechanics (QM) and MM (QM/MM) have been carried out to investigate the product specificity and mechanism of the histone H4 lysine 20 (H4-K20) methylation by human histone lysine methyltransferase SET8. At neutral pH, the target lysine is available to only the enzyme in the protonated state. The first step in the methylation reaction must be deprotonation of the lysine target which is followed by the (+)AdoMet methylation of the neutral lysine [Enz.Lys-CH(2)-NH(3)(+).(+)AdoMet --> H(+) + Enz.Lys-CH(2)-NH(2).(+)AdoMet -->--> Enz.Lys-CH(2)-N(Me)H(2)(+).AdoHcy]. The electrostatic interactions between two positive charges on (+)AdoMet and Lys20-NH(3)(+) decrease the pK(a) of Lys20-NH(3)(+). Upon formation of Enz.Lys-NH(3)(+).(+)AdoMet, a water channel by which the proton escapes to the outer solvent phase is formed. The formation of a water channel for the escape of a proton from Lys20-N(Me)H(2)(+) in Enz.Lys20-N(Me)H(2)(+).(+)AdoMet is not formed because the methyl substituent blocks the starting of the water channel. Thus, a second methylation does not take place. The dependence of the occurrence of methyl transfer on the formation of a water channel in SET8 is in accord with our previous reports on product specificity by histone lysine monomethyltransferase SET7/9, large subunit lysine dimethyltransferase (LSMT), and viral histone lysine trimethyltransferase (vSET). The average value of the experimental DeltaG(E)() for the six lysine methyl transfer reactions catalyzed by vSET, LSMT, and SET7/9 with p53 as a substrate is 22.1 +/- 1.0 kcal/mol, and the computed average (DeltaG(C)()) is 22.2 +/- 0.8 kcal/mol. In this study, the computed free energy barrier of the methyl transfer reaction [Lys20-NH(2) + (+)AdoMet --> Lys20-N(Me)H(2)(+) + AdoHcy] catalyzed by SET8 is 20.8 kcal/mol. This is in agreement with the value of 20.6 kcal/mol calculated from the experimental rate constant (0.43 +/- 0.02 min(-1)). Our bond-order computations establish that the H4-K20 monomethylation in SET8 is a concerted linear S(N)2 displacement reaction.
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PMID:Product specificity and mechanism of protein lysine methyltransferases: insights from the histone lysine methyltransferase SET8. 1851 60

In order to illustrate the clinical and histological presentations of laryngeal atypical carcinoids and their potential course, we report six cases. We evaluated the factors predictive of local recurrence and metastatic diffusion. For each case, we noted the mitotic index, the quality of the resection, the limits of the tumor and the presence of necrosis. An immunohistochemical study was carried out with a series of antibodies (cytokeratins; D(2)40; CD31; MIB1; P53; P16; TTF1...). The clinical presentation we observed was quite similar to that reported in the literature. These tumors are CK7+, CK8+, CK19+, CK5-6-, CK14- and CK20-. P16 is constantly positive. Only the mitotic index and the lymphatic presence of embolus were correlated with the time course. The tumor is more aggressive when the mitotic index is high and an unfavorable course is observed when there are lymphatic emboli or when the Ki67 index is higher than 5%.
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PMID:[Atypical carcinoid of the arytenoid: report of six cases]. 1853 8

Small cell carcinoma of the urinary bladder is a rare entity known as an aggressive tumor. As it is rarely associated with transitional cell carcinoma in situ but more commonly with invasive transitional cell carcinoma, its origin is not well understood. We report a case of small cell carcinoma with coexisting transitional cell carcinoma in situ, where histologic mapping and parallel immunohistochemical and molecular analyses (TP53 mutation analyses, loss of heterozygosity) were performed. Immunohistochemical characterization (synaptophysin, thyroid transcription factor-1, chromogranin A, neuron specific enolase, CD56, CK, CK7, CK20, CD44v6, and p53) emphasized the morphology. Identical point mutations of TP53 were identified in invasive small cell carcinoma and transitional cell carcinoma in situ. No loss of heterozygosity of microsatellite markers D3S3050, D9S303, D9S304, D9S171, D9S775, D9S1748, D9S1751, D17S786, D17S918, and TP53alu was found in either component. We provide, for the first time, molecular evidence for the development of invasive small cell carcinoma out of transitional cell carcinoma in situ.
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PMID:Insights from a whole cystectomy specimen--association of primary small cell carcinoma of the bladder with transitional cell carcinoma in situ. 1854 17

Foamy gland adenocarcinoma is a variant of pancreatic ductal carcinoma, whose precursor has not been described. We describe here the morphologic and immunohistochemical features of the pancreatic intraepithelial neoplasia (PanIN) lesions associated with invasive foamy pancreatic adenocarcinoma. The staining properties and morphologic and immunohistochemical features of 3 foamy PanIN lesions were compared with those of 7 pancreatic foamy gland adenocarcinomas. Hematoxylin and eosin, Mayer mucicarmine, periodic acid-Schiff, and Alcian blue stains were available for review in all cases. Immunohistochemical labeling for cytokeratin (CK)7, CK20, carcinoembryonic antigen polyclonal, MUC1, MUC2, CDX2, p53, and cyclin D1 was performed. The PanIN-1 lesions were found in the nonneoplastic pancreas and were similar to the PanIN-1 lesions of ordinary pancreatic ductal carcinoma. The PanIN-2 and -3 lesions were recognized immediately adjacent to or within the invasive foamy gland carcinoma. In these lesions, small or markedly dilated ducts were lined by cuboidal and columnar dysplastic nonfoamy cells and foamy cells. Hobnail cells were present in 2 cases. The PanIN-1, 2, and 3 lesions and the invasive foamy gland adenocarcinomas stained with mucicarmine, periodic acid-Schiff, and Alcian blue. The 3 PanIN-2 and -3 lesions and all 7 invasive foamy adenocarcinomas labeled with CK7, carcinoembryonic antigen polyclonal, and MUC1, whereas only 2 PanIN-2 and -3 lesions and 5 invasive adenocarcinomas showed immunoreactivity for cyclin D1 and p53. Three distinctive foamy PanIN lesions were identified within 7 invasive foamy gland pancreatic adenocarcinomas. The gradual progression of cytological and architectural abnormalities of the PanIN lesions from PanIN-1 to PanIN-3 excludes neoplastic ductal spread. These foamy PanIN lesions probably represent cancer precursors.
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PMID:The foamy variant of pancreatic intraepithelial neoplasia. 1862 Sep 91


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