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)

The purpose of this study was to evaluate the role of angiogenesis, proliferative activity (assessed by Ki-67 expression), p53 and ras-oncogene (H-ras) expression, and conventional clinicopathologic factors in predicting overall survival rates in patients with pancreatic ductal adenocarcinoma. We followed-up 22 patients with ductal adenocarcinoma of the pancreas for a median of 19 months (range, 2 to 44 months). Angiogenesis was quantitated as vascular surface density (VSD) and the number of vessels per mm2 stroma (NVES) after microvessels were immunostained, using factor VIII-related antigen. p53, H-ras, and Ki-67 proteins were also determined immunohistochemically. VSD and NVES showed significant correlations with increased proliferative activity, poor tumor differentiation, and tumor size of 3 cm or more (P = 0.001, P = 0.013, and P = 0.047, respectively). The overall 2-year survival rate of 33.3% in patients with high VSD and NVES values was significantly worse than that of 66.6% estimated in patients with low microvessel count (log rank, 3.97; P = 0.046). In multivariate analysis using the Cox model, VSD was found to be an independent prognostic factor of survival (P = 0.039). H-ras and p53 expressions were not correlated with angiogenesis parameters. We conclude that, in pancreatic ductal adenocarcinoma, angiogenesis is closely related to tumor growth and patient survival.
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PMID:Tumor angiogenesis as a prognostic predictor in pancreatic cancer. 1118 Aug 76

Immunohistochemical analysis of the expression of transforming growth factor alpha (TGF-alpha) and its receptor, epidermal growth factor receptor (EGFR), was performed in a series of 86 invasive carcinomas of the breast. TGF-alpha immunostaining was observed in the majority of the cases (72.1%), both in epithelial cells and in adjacent stromal cells. EGFR was also present in tumors (34.2%) and in the endothelial cells (46.1% of the cases) near the tumors. A significant association was observed between TGF-alpha expression and angiogenesis evaluated by immunohistochemistry using an antibody against factor VIII-related antigen. No association was observed between TGF-alpha expression and other clinicopathologic features. In contrast, EGFR expression in the tumor was associated with features of poor prognosis, such as tumor size, histologic grade, lymph node status, estrogen receptor content, p53 expression, sialyl-Tn expression, and age. The presence of EGFR in endothelial cells was correlated to young patient age. We also observed an association of EGFR in endothelial cells and angiogenesis in tumors with a size of less than 2 cm. Inversely, in larger tumors, angiogenesis was only associated with tumor TGF-alpha expression. These results indicate that endothelial EGFR may play a role in the early steps of breast cancer angiogenesis.
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PMID:Expression of TGF-alpha and EGFR in Breast Cancer and its Relation to Angiogenesis. 1134 60

We report a case of gliosarcoma with areas of primitive neuroepithelial differentiation arising in the temporal lobe of a 53-year-old man. The sarcomatous component of this tumor was perivascular in its distribution and showed expression of factor VIII-related antigen, smooth muscle actin and CD34. The primitive neuroepithelial component possessed a small cell morphology and showed expression of neuronal antigens. Strong expression of p53 was demonstrated throughout the tumor with only focal weak expression of epidermal growth factor receptor. The tumor developed widespread extraneural metastases 5 months after surgical resection of the primary tumor. Histological examination of the liver metastases showed them to consist predominantly of the primitive neuroepithelial component. We believe this to be a novel pattern of differentiation in a gliosarcoma which in this case was associated with an aggressive metastatic potential.
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PMID:Gliosarcoma with areas of primitive neuroepithelial differentiation and extracranial metastasis. 1214 29

Due to the fact that capillary vessels provide not only supply of nutrients to the tumor but also represent a gate for lymphogenous and hematogenous metastatic spreading of the tumor, angiogenesis has gained increasing attention in recent years. The aim of the project was: 1. to study number of capillaries in the tumor and its relationship to the metastatic potency and prognosis and 2. to analyse the differences in the quantity of the capillaries between the groups of tumors with or without previously performed aspiration biopsy. 142 cases of breast carcinoma diagnosed at the Fingerland's Department of Pathology in the years 1997-98 were examined. Endothelial cells were visualized immunohistochemically using an antibody against factor VIII (von Willebrand factor). Capillary vessels were counted at 200x magnification (using eyepiece graticule) in the areas of highest angiogenic activity (hot spots), usually at the periphery of the tumor. The highest microvessel counts (HMC) were correlated with other factors (age, tumor size, grade, nodal status, expression of hormonal receptors, proliferative activity, p53, HER-2/neu). The differences between the tumors with and without previous aspiration biopsy were analyzed. All patients were women aged 31-86 years (median 59). The size of tumors was 4-70 mm (median 20 mm). Sixty cases have been previously examined by fine needle aspiration cytology; 72 cases were node-positive. HMC values varied from 26 to 185 (average 63.9, median 60) per microscopic field (area 0.24 mm2). The HMC was significantly higher in node-positive tumors (median 57.5 versus 66; p = 0.036). The capillary vessel counts did not correlate with other parameters examined. Fine needle aspiration cytology does seem to increase the number of intratumoral capillary vessels only for a transitory period. We have also compared HMC/mm2 in normal breast tissue with counts in carcinoma. Interestingly, the values in normal lobules, were significantly higher (median 565 versus 243; p < 0.0000001).
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PMID:[Angiogenesis in breast carcinoma. Immunohistochemical study of 142 cases]. 1166 26

The objective of this study was to evaluate the possible prognostic significance of p53 protein overexpression and tumor angiogenesis (TA) in nasopharyngeal carcinoma (NPC) patients, together with other clinicopathological variables. Forty-two NPC patients were evaluated in relation to survival. Nuclear p53 overexpression in neoplastic and endothelial cells was detected by immunohistochemistry (IHC) with the monoclonal antibody DO-7 and the polyclonal antibody against factor VIII-related antigen, respectively. Thereafter, we evaluated p53 cases in order to determine their nuclear immunoreactivity from negative (-) to positive (+, ++, +++). In addition, microvessels were counted in the most active areas of tumor neovascularization or hotspots using an image computer analyzer (MicroImage). A Cox multiple regression survival analysis was used to determine the best prognostic indicators in NPC patients. As a result, tumor microvessel count, considered as a continuous variable, was the most important independent prognostic indicator in relation to survival (p = 0.0273), with a relative risk of death of 2,4399 [95% confidence interval = 1.1051 ; 5.3871] associated with the highest microvessel counts. Moreover, the only clinicopathological variable that demonstrated prognostic value in a Cox multiple regression survival analysis was histological type (p = 0.05). In addition, we did not observe any statistical association between intratumoral microvessel density (IMD), clinicopathological variables and p53 protein expression.
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PMID:Expression of p53 protein and tumor angiogenesis as prognostic factors in nasopharyngeal carcinoma patients. 1192 71

Riddelliineis a naturally occurring pyrrolizidine alkaloid found in certain poisonous rangeland plants of the western United States. In National Toxicology Program 2-year studies, riddelliine induced high incidences of hemangiosarcoma in the liver of F344/N rats (both sexes) and B6C3F1 mice (males). To understand this pathogenesis, we tested short-term effects of riddelliine. Three groups (control; 1.0 mg/kg/day, high dose used in the 2-year study; and 2.5 mg/kg/day) of seven male F344/N rats per group were terminated after 8 consecutive doses and 30 doses (6 weeks, excluding weekends). Serum vascular endothelial growth factor (VEGF), histological, immunohistochemical [factor VIII-related antigen/von Willebrand factor (fVIII-ra/vWf)], VEGF, VEGF receptor-2 (VEGFR2), glutathione S-transferase-pi, S-phase (BrdU), p53, apoptosis, and ultrastructural evaluations were performed on the liver. Following 8 doses of 1.0 and 2.5 mg/kg/day, increased numbers of apoptotic and S-phase nuclei appeared in hepatocytes and endothelial cells. Following 30 doses of 1.0 and 2.5 mg/kg/day, hepatocytes exhibited reduced mitosis, fewer S-phase nuclei, increased hypertrophy, and fatty degeneration, while endothelial cells showed karyomegaly, cytomegaly, decreased apoptosis, more S-phase nuclei, and p53 positivity. Hepatocytes of treated animals expressed higher VEGF immunopositivity. That altered endothelial cells were fVIII-ra/vWf and VEGFR2 positive confirmed their identity. These changes may have promoted hemangiosarcoma development upon long-term exposure through endothelial adduct formation, apoptosis, proliferation of endothelial cells having undamaged and/or damaged DNA, and mutation. Endothelial proliferation may also have been promoted through endothelial arrest at S phase, which was associated with endothelial karyo- and cytomegaly, resulting in hepatocytic hypoxia, triggering VEGF induction.
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PMID:The hepatic endothelial carcinogen riddelliine induces endothelial apoptosis, mitosis, S phase, and p53 and hepatocytic vascular endothelial growth factor expression after short-term exposure. 1246 Jul 43

This study was undertaken to examine the interaction between the combination of angiogenesis and blood vessel invasion (BVI) and haematogenous metastasis, and to determine the prognostic significance of that combination in predicting 20-year relapse-free survival (RFS) and overall survival (OS) rates in primary breast cancer. Five hundred and nine patients were studied. We investigated 11 factors, including average microvessel count (AMC)/BVI, lymph-node status (n), clinical tumour size (T), histological grade (HG), lymphatic vessel invasion (LVI), p53, proliferating cell nuclear antigen (PCNA), c-erbB-2, mitotic index (MI), apoptotic index, and tumour necrosis (TN). Blood vessel invasion was detected by both factor VIII-related antigen and elastica van Gieson staining. To evaluate the best objective method to quantify microvessel density in angiogenesis, AMC was employed. The rate of AMC-high and BVI-positive tumours was 32.6 and 29.3%, respectively. That of both AMC-high and BVI-positive tumours was 10.1%. Univariate analysis showed that AMC/BVI, n, T, HG, LVI, p53, PCNA, MI, and TN were significantly predictive of RFS and OS. By multivariate analysis, AMC/BVI was the strongest independent prognostic factor for 20-year RFS (relative risk (RR)=5.5; P<0.0001) and for 20-year OS (RR=4.3; P<0.0001). Lymph-node status was still considered a powerful prognostic indicator; however, the combination of AMC and BVI provided more reliable prognostic information than lymph-node status for haematogenous dissemination.
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PMID:The combination of angiogenesis and blood vessel invasion as a prognostic indicator in primary breast cancer. 1279 34

In this study 65 primary malignant fibrous histiocytomas (MFH) of high malignancy grade were characterized by immunohistochemistry for their expression of proteins reflecting or promoting tumor growth. The results were evaluated in relation to the disease-free survival and the occurrence of metastases alone or in combination with local recurrences during follow-up. A tumor size >8 cm was strongly associated with both a shorter disease-free survival (p=0.001) and a higher frequency of metastases alone or together with local recurrence during follow-up (p=0.001 and 0.004). Similarly a higher frequency of mitosis was associated with a shorter disease-free survival (p=0.004), while the presence of necrosis or malignancy grade 4 did not affect the clinical outcome. No significant effect on the clinical outcome was seen for p53, Ki-67, p27 expression or for vascular density determined by factor VIII staining. However, a significant association was demonstrated between high Bcl2 expression and the risk to develop both local recurrence and metastases (p=0.026). Taken together, the findings support the importance of the tumor size, and suggest that bcl2 staining but not p53, Ki-67, p27, vascular density or distinction of grade 3 and grade 4 tumors are of clinical value in the prognostication of MFH tumors.
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PMID:Evaluation of immunohistochemical parameters as prognostic markers in malignant fibrous histiocytoma. 1288 52

Thymidine phosphorylase (TP) is a unique enzyme involved not only in angiogenesis, but in 5-fluorouracil (5-FU) metabolism as well. TP is produced by both tumor and stromal cells. The aim of this study was to reveal the clinical implication of TP localization in tumor tissues. Advanced colorectal cancer specimens (n=97) were prepared for immunohistochemical staining using monoclonal antibodies against TP, p53, vascular endothelial growth factor (VEGF), factor VIII, CD68 and thymidylate synthase (TS). Clinicopathological factors and the clinical prognosis were examined for each indicator. High tumor TP expression and high stromal TP expression were observed in 38% (36/95 cases) and 49% (47/95 cases) of the cases, respectively. High tumor TP expression tended to correlate with microvessel density (MVD) (p=0.0511). Among patients who underwent curative resection, those with high stromal TP expression had a favorable prognosis (p=0.0127). High stromal TP status was also a strong prognostic factor in the group receiving adjuvant 5-FU derivatives (p=0.0222). TP produced by tumor cells has a stimulatory effect on tumor angiogenesis, while that produced by stromal cells plays an entirely different role. The latter may enhance the anticancer effect of 5-FU via its catalyzed function.
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PMID:Importance of thymidine phosphorylase expression in tumor stroma as a prognostic factor in patients with advanced colorectal carcinoma. 1570 8

A 59-year-old man presented with a 10-cm x 8-cm tumoral plaque with a superficial nodule in the interscapular region of the back (Fig. 1). The lesion had been growing for 25 years. As a cystic lesion was suspected, the superficial nodule was biopsied. The histopathologic diagnosis was low-grade sarcoma with sclerosis. Two months after the initial biopsy, the lesion was completely excised, reaching the muscular fascia, with a 2-cm margin and with a free graft. Formalin-fixed paraffin-embedded samples were submitted to histologic and immunohistochemical study (4-microm paraffin sections); frozen tissue was submitted to electron microscopy. For histopathology, sections were stained with hematoxylin and eosin. Immunohistochemistry was performed following standard avidin-biotin immunoperoxidase procedures with primary antibodies for vimentin, CD34, smooth muscle-specific actin, bcl-2, S-100, desmin, myoglobin, factor VIII, p53 (all from DAKO, Copenhagen, Denmark), HHF-35 (Enzo Diagnostics, Farmingdale NY), cytokeratin (AE1/AE3) (Biogenex, San Ramon, CA), and factor XIIIa (Calbiochem Novabiochem Corporation, La Jolla, CA). At low magnification, the histologic study of the initial tumoral nodule revealed a poorly circumscribed mesenchymal proliferation, with fibroblastic-like neoplastic cells arranged in a fascicular and storiform pattern, admixed with extensive areas of sclerosis. At higher magnification, tumoral cells were spindle-shaped with hyperchromatic nuclei and scant cytoplasm. In some areas, sclerosis was so evident that a keloid-like pattern was seen (Fig. 2a). The surgical specimen showed a fibroblastic neoplastic proliferation infiltrating the dermis and hypodermis. In the dermis, cells were arranged in a storiform pattern, whereas in the hypodermis there was a honeycomb or lace-like pattern (Fig. 2b). There were also cellular areas alternating with sclerotic areas, with transitional zones in between, in both the dermis and hypodermis. The immunohistochemical study of the initial tumoral nodule and the surgical specimen showed that tumoral cells expressed vimentin, CD34 (Fig. 3), bcl-2, HHF-35, and smooth muscle actin. Neoplastic cells failed to show positivity with desmin, myoglobin, factor XIIIa, factor VIII, S-100, cytokeratin (AE1/AE3), and p53. An ultrastructural study revealed spindle cells having an irregular contour with a well-developed granular reticulum endoplasmic (REG) system in their cytoplasm, as well as some Golgi complexes and mitochondria. Also visible was the presence of many actin filaments and some myosin condensations (Fig. 4), characteristics of a fibroblastic cell with myofibroblastic differentiation. The final histopathologic diagnosis of the surgical specimen was sclerosing dermatofibrosarcoma protuberans. Two years after surgery, the patient is alive and well.
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PMID:Sclerosing dermatofibrosarcoma protuberans (DFSP): an unusual variant with focus on the histopathologic differential diagnosis. 1642 80


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