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

The cell cycle of multicellular organisms must be tightly coordinated with organogenesis and differentiation. Experiments done in vitro have identified chromatin assembly factor 1 (CAF-1) as a protein complex promoting chromatin assembly during DNA replication, but the in vivo role of CAF-1 in multicellular animals is still poorly understood. Here we describe the characterization of a zebrafish mutant disrupting CAF-1b activity, and show that it leads to defective cell cycle progression and differentiation in several organs, including the retina, optic tectum, pectoral fins, and head skeleton. Retinal precursor cells mutant for caf-1b arrest in S phase and undergo p53-mediated apoptosis. While p53 deficiency is able to rescue apoptosis in caf-1b mutants, it fails to rescue differentiation, indicating that CAF-1 activity is essential for differentiation in these organs. In addition, we also show that regulation of caf-1b expression in the retina depends on a group of genes that regulate the switch from proliferation to differentiation.
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PMID:Mutation of zebrafish caf-1b results in S phase arrest, defective differentiation, and p53-mediated apoptosis during organogenesis. 1815 5

We present the surgical and pathological findings and follow-up of 5 women diagnosed with combined endometrioid and high-grade neuroendocrine carcinoma of large cell type (LCNEC) arising in the endometrium. The mean age of the women was 75 years (range, 50-88 years). Of the 5 tumors, 4 formed polypoid endometrial masses associated with extensive lymphovascular involvement of the myometrium by neoplastic cells. A single endometrial tumor was formed by LCNEC alone, and 4 tumors were composite with varying proportions formed by endometrioid (4/5) and small cell neuroendocrine carcinoma (1/5). In all 5 LCNEC tumor components, an insular growth pattern was noted, whereas a diffuse (solid) pattern was found in 4 tumors, a trabecular in 2, and rosettes/pseudorosettes in another 2. In all 5 tumors, the LCNEC tumor components were labeled with neuron-specific enolase (NSE). Four tumors were reactive for chromogranin A, CAM 5.2, and p53. Three tumors were labeled for AE1/AE3, CD56 (NCAM), p16, and cytokeratin 7. Synaptophysin was reactive in 2 tumors, and CD117 was found in only a single tumor. Of the 3 endometrioid tumor components examined, all were reactive for NSE. Two tumors were reactive for p16 and p53, 1 for CD56, but none for synaptophysin orchromogranin A. We conclude that LCNEC of the endometrium is a distinct clinicopathological entity with a poor prognosis irrespective of stage. The gross and histomorphological features are often suggestive, but confirmation requires immunoperoxidases, including NSE, synaptophysin, chromogranin A, p16, and p53. Combined endometrioid and high-grade LCNEC possess more characteristics of a type II than a type I endometrial carcinoma.
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PMID:Combined large cell neuroendocrine and endometrioid carcinoma of the endometrium. 1815 75

Carcinosarcomas are malignant tumors with a mixture of carcinomatous and differentiated sarcomatous elements. We investigate the morphology, immunohistochemistry, and comparative genomic hybridization analysis of 3 mixed squamous carcinoma and osteosarcoma of the lung. All patients were male and their ages were 72, 43, and 58 years. The sizes of the neoplasms were 7, 5, and 5 cm in maximum diameter, respectively. Two patients died of the disease 9 and 14 months after surgery; and one is alive 6 months later. By light microscopy, all cases had both squamous and osteosarcomatous structures. Immunohistochemistry was positive for AE3AE1, p63, 34 E12, CAM 5.2 (2/3 cases), CK-7 (2/3 cases), epithelial membrane antigen, E-cadherin, p53, and carcinogenic embryonic antigen in carcinomatous areas, and for vimentin and CD-68 in sarcomatous component. Areas of transition positive for both cytokeratins and vimentin were seen in all cases. A total of 55 copy number changes were detected with a median of 18 abnormalities per case: 48 gains, 6 losses, and 1 high-level amplification. Chromosome alterations in osteosarcomatous areas were similar to those found in lung metastatic osteosarcoma, comparable to those found in carcinomatous areas and to lung squamous carcinomas. Coincidences between carcinomatous areas and osteosarcomatous zones were found as gains in chromosomes 1q, 3q, 5p, 8q, and 12p. These findings provide arguments that favor a common origin for both types of cells, supported by the mixture of cells, the existence of undifferentiated cells positive to both cytokeratin and vimentin markers, and the CGH overlaps of chromosomal gains between carcinomatous and sarcomatous areas.
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PMID:Primary mixed squamous carcinoma and osteosarcoma (carcinosarcomas) of the lung have a CGH mapping similar to primitive squamous carcinomas and osteosarcomas. 1838 57

Chloramphenicol is a broad-spectrum antibiotic used for the treatment of many infectious diseases and has become one of the major seafood contaminants. Hematologic disorders such as aplastic anemia and leukemia induced by chloramphenicol are a major concern. However, the mechanism underlying chloramphenicol-induced leukemogenesis is not known. By investigating the effects of chloramphenicol on the activation of mouse T cells stimulated with anti-CD3 antibody or staphylococcal enterotoxin B, we found that chloramphenicol induces the differentiation of activated T cells into lymphoblastic leukemia-like cells, characterized by large cell size, multiploid nuclei, and expression of CD7, a maker for immature T cells and T-cell lymphocytic leukemia, thus phenotypically indicating differentiation toward leukemogenesis. High expression of cyclin B1, but not p53, c-myc, and CDC25A, was detected in chloramphenicol-treated activated T cells, which may relate to abnormal cell differentiation. Chloramphenicol inhibited the activation-induced cell death of mouse and human T-cell receptor-activated T cells by down-regulating the expression of Fas ligand. Our findings show that abnormal cell differentiation and inhibition of apoptosis may contribute to the development of leukemia associated with clinical applications of chloramphenicol.
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PMID:Chloramphenicol induces abnormal differentiation and inhibits apoptosis in activated T cells. 1855 35

Poly(ADP-ribosyl)ation of transcription factors and coregulators, mediated by the poly(ADP-ribose) polymerase PARP-1, has been emerging as an important epigenetic mechanism that controls transcriptional dynamics in response to diverse intra- and extracellular signals. PARP-1 activity is also implicated in the regulation of mammalian lifespan. Herein we show that transcriptional down-regulation of androgen receptor (AR) in the aging rat liver and in oxidatively stressed hepatoma cells involves exchange of a PARP-1-associated, p/CAF-containing coactivator assembly for a p53-interacting, Groucho/TLE1-, and mSin3A-included corepressor complex at an age- and oxidant-responsive DNA element (age-dependent factor (ADF) element) in the AR promoter. The coregulator switch is mediated by B-Myb and c-Myb, which bind to the ADF element and physically associate with PARP-1 and the tumor suppressor p53. Heterogeneous nuclear ribonucleoprotein K, residing at the ADF element in association with PARP-1, may serve a platform role in stabilizing the activating complex. PARP-1 coactivated B-Myb- and c-Myb-mediated transactivation of the AR promoter, and p53 antagonized the B-Myb/c-Myb-induced AR promoter activation. PARP-1, heterogeneous nuclear ribonucleoprotein K, B-Myb, and c-Myb each serves as a positive regulator of cellular AR content, whereas p53 negatively regulates AR expression. Our results identify a shared, PARP-1-regulated sensing mechanism that coordinates transcriptional repression of AR during aging and in response to oxidative stress. This study may provide insights as to how advancing age and intracellular redox balance might influence androgen-regulated physiology.
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PMID:Loss of androgen receptor in aging and oxidative stress through Myb protooncoprotein-regulated reciprocal chromatin dynamics of p53 and poly(ADP-ribose) polymerase PARP-1. 1894 70

We present the clinicopathological features of eight cases of large cell undifferentiated bladder carcinoma not otherwise specified (LCUBC). LCUBC was characterised by sheets of large polygonal or round cells with moderate to abundant cytoplasm and distinct cell borders. The LCUBC component varied from 90 to 100% of the tumour specimen with five cases showing pure LCUBC. The architectural pattern of the tumour varied from infiltrating tumour to solid expansile nests with focal (<5%) discohesive growth pattern in two cases. Immunohistochemical staining demonstrated that LCUBC cases were positive for cytokeratins AE1/AE3 and 7; CAM 5.2, CK20, thrombomodulin and uroplakin III were positive in six, three, three and two cases, respectively. Other immunohistochemical markers performed in the differential diagnosis context included alpha-fetoprotein, beta human chorionic gonadotrophin (betahCG), prostate specific antigen (PSA), vimentin, synaptophysin and chromogranin and all were negative. Ki-67 and p53 labelling indexes were 50-90% and 40-90%, respectively. All patients had advanced stage cancer (>or=pT3) and seven (87.5%) had lymph node metastases. Follow-up information was available in all cases, with a range of 6-26 months (mean 10.6 months). Six patients died of disease between 5 and 26 months and two patients were alive with metastases at 6 and 14 months. The prognosis of LCUBC was compared with conventional urothelial carcinoma of similar stages showing survival differences (p =0.0004). In summary, LCUBC is an aggressive variant of urothelial carcinoma that presents at an advanced stage.
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PMID:Large cell undifferentiated carcinoma of the urinary bladder. 2043 10

This review summarizes biological markers of head and neck cancer, which have emerged from recent developments in molecular changes during carcinogenesis. These markers could be evaluated in every step that is believed to be necessary for the development of a cancer: acquisition of autonomous proliferative signalling (EGFR), proliferative activity of tumour cells (DNA content, Ki-67, mitotic index), inhibition of growth inhibitory signals (Bcl-2), apoptosis (p53), immortalization (telomerase), angiogenesis (CD34, VEGF) and metastasis (MMP-9, E-cadherin, I-CAM aj.). Most of these biological markers are at the preclinical research stage. Significant progress has been achieved in the application of targeted therapy in head and neck cancer.
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PMID:[Molecular predictors in head and neck tumours]. 2080 19

Small cell carcinoma (SC) of the gallbladder is an uncommon tumor, and not enough information of this tumor has been previously reported. The SCs in this series occured in nine women and six men (mean age; 64.5 years). Histologically, they consisted of small atypical cells with scanty cytoplasm, hyperchromatic nuclei and inconspicuous nucleoli growing in sheets and cords. Two tumors contained neoplastic glands similar to those of well-differentiated adenocarcinoma and a histological transition between SC and adenocarcinoma was seen in one of the two tumors. Argyrophil granules were present in 10 tumors. The tumor cells were immunoreactive to epithelial markers (epithelial membrane antigen: 12/14; AE1/AE3: 12/14; CAM 5.2: 9/14; carcinoembryonic antigen: 7/14) and neuroendocrine markers (neuron specific enolase: 11/14; chromagranin A: 4/14; Leu 7: 10/14; adrenocorticotrophic hormone: 6/14). Abnormalities in tumor suppressor gene p53 expression were found in 9 of 14 SCs by using monoclonal antibody PAb 1801. Flow cytometry revealed aneuploidy in 7 (78%) of 9 in the SC and 26 (40%) of 65 in the adenocarcinoma. The survival curve of the SCs was less favorable than that of papillary adenocarcinoma and well differentiated adenocarcinoma in pTNM stage 2-4 (P=0.0027, P=0.0017, respectively). These results suggested that the SCs of the gallbladder arose from common primitive cells capable of endocrine and epithelial differentiation, while most SCs (78%) showed DNA aneuploid by flow cytometry and their prognosis was worse than that of differentiated adenocarcinoma of the gallbladder.
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PMID:Small-cell carcinoma of the gallbladder - a clinicopathological, immunohistochemical and flow cytometric study of 15 cases. 2157 51

Co-amplification of the centromere on chromosome 17 (CEP17) and HER2 can occur in breast cancer. Such aberrant patterns (clusters) on CEP17 can be misleading to calculate the HER2/CEP17 ratio, and thus underreporting of HER2 amplification. We identified 14 breast cancers retrospectively with HER2/CEP17 co-amplification and performed FISH (fluorescence in situ hybridization) with additional chromosome 17 probes (17p11.1-q11.1, 17p11.2-p12, TP53 on 17p13.1, RARA on 17q21.1-3 and TOP2 on 17q21.3-22) to characterize the spanning of the amplicon in these cases. Furthermore, the HER2 status was analyzed by means of HER2 silver in situ hybridization (SISH) and immunohistochemistry (IHC). The co-amplification of HER2/CEP17 was compared between the three institutions. TP53 was eusomic in all cases, 17p11.2-p12 in 79% (11/14), whereas 17p11.1-q11.1 showed chromosomal gain in all cases. RARA was amplified in 10/14 cases (71%) and TOP2 in 3/14 cases (21%). HER2 was amplified with FISH/SISH in all 14 cases. 9/14 tumors were 3+ IHC positive (64%) and 3 cases were 2+ IHC positive. In our cohort the CEP17 amplicon almost always involves the HER2 but not the TOP2 locus. Overall agreement on HER2/CEP17 ratio (when applying ASCO/CAP guidelines) was only 64% (9/14 cases) between the institutions. Discrepant ratios varied from 1.1 to 14.3. The HER2/CEP17 co-amplification is not defined in the ASCO/CAP guidelines, and may result in inaccurate HER2-FISH/SISH status, particularly if only the calculated HER2/CEP17 ratio is reported. It is recommended to report separate CEP17 and HER2 signals in complex HER2/CEP17 patterns.
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PMID:Co-amplification of the HER2 gene and chromosome 17 centromere: a potential diagnostic pitfall in HER2 testing in breast cancer. 2169 7


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