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)

Although most papillary thyroid microcarcinomas (PMCs) are of little clinical significance, patients with PMCs occasionally have an unfavorable outcome, especially when they present with bulky nodal metastasis or distant metastasis. We have attempted to identify "high-risk" PMCs by evaluating clinical, pathologic, and immunohistochemical prognostic factors. Among 190 patients with a PMC, 156 without clinically apparent nodal metastasis had a benign course. The remaining 34 patients, who presented with cervical lymphadenopathy of at least 1 cm, were studied. Three of the four patients who developed distant metastasis died of the disease, and the other died of local recurrence. All patients who developed distant metastasis or died of the disease had both nodal metastasis of at least 3 cm and a nonencapsulated type of primary lesion. All patients who developed distant metastasis showed both extracapsular extension of the metastatic lesions in lymph nodes and positive staining for transforming growth factor-beta3 (TGFbeta3) (a potent growth inhibitor) in the primary lesion. The Ki-67 (an indicator of cell proliferation) labeling indices in the primary and metastatic nodal lesions of patients who died of cancer were significantly higher than those of the others with nonfatal disease. None of the patients showed P53 (nuclear tumor-suppressor phosphoprotein) overexpression. In conclusion, patients with PMC who have both 3 cm or larger lymphadenopathy and a nonencapsulated type of primary lesion may be regarded as high-risk patients. Immunohistologic positivity for Ki-67 and TGFbeta3 in cancer cells is a potential indicator of aggressively malignant PMC.
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PMID:Clinicopathologic and immunohistochemical studies of papillary thyroid microcarcinoma presenting with cervical lymphadenopathy. 960 90

Tumor size, axillary nodal status, histologic grading and the hormonal receptor status are the established prognostic factors for breast carcinoma. Concurrent to these factors the clinical validation of the new innovative tumor characteristics from molecular biology is difficult to achieve. Clinicians are more and more interested in indicators of response to particular treatments (predictive factors) and less in prognostic factors relevant for the natural course. The hormonal receptor status is the best known predictive factor with regard to the response to hormonal treatment. Among the innovative parameters the tumor suppressor gene p53 and the oncogene Her2/neu show a good correlation to sensitivity to cytostatic treatment. The detection of more and more molecular mechanisms of tumor growth and tumor spread raise hopes that innovative treatment approaches will lead to an antineoplastic effect. The molecular tumor parameters then may play the role of predictive factors for a specific treatment. For the present the established tumor factors should be used as the base for a treatment plan and the available already known predictive factors should be taken into consideration.
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PMID:[Relative indicators for disease outcome in breast carcinoma]. 960 45

In esophageal squamous cell carcinoma, p53 gene mutations have been analyzed for inter- or intra-patient heterogeneity but only a few studies have investigated intratumoral heterogeneity. We investigated this question within individual esophageal cancers, and also in their lymph-node metastases in 8 cases. Analyzing the p53 gene sequence by direct sequencing of polymerase chain reaction products, we found heterogeneity for p53 mutations in the pre-invasive area in 3 esophageal cancers. In all areas sampled in the invasive portion of each cancer, the p53 mutational status was identical in a given tumor. In heterogeneous tumors, the invasive area showed one of the p53 mutations found in the pre-invasive area. In nodal metastases, the p53 mutation was identical to that in the invasive area of each primary tumor. These data suggest that the timing of p53 alteration is not as early as might have been expected, indicating that, in regard to p53 gene alteration, some esophageal cancers are composed of various subclones in the pre-invasive stage with invasiveness developing in one of them, which becomes predominant through clonal selection.
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PMID:Heterogeneity of p53 mutational status in esophageal squamous cell carcinoma. 961 46

VLA2 is thought to be involved in the metastatic process in malignant tumours, in particular in carcinomatous cell adhesion to vessel basement membrane. VLA2 expression was immunohistochemically investigated in 204 breast carcinomas. Frozen tissue sections were probed with monoclonal anti-VLA2 using automated (Ventana ES 320 System) and quantitative (SAMBA 2005 image processor) immunoperoxidase. A positive anti-VLA2 immunoreaction was observed in 48 tumours (23.5%), within epithelial carcinomatous cells. The VLA2-positive surface in tumours varied from 3% to 20% (mean 8.75, S.D. 7.17) and was correlated with histoprognostic indicators and tumour expression of various antigens detected using the same method as that for VLA2. The results show that VLA2 immunoexpression was independent of the tumour size, grade, type and aneuploidy, and of the nodal status. VLA2 significantly correlated with ELAM, VCAM, VLA3 and P-glycoprotein (P-gp) (P < 0.01) and inversely correlated with cathepsin D (P < 0.001), but was independent of Ki67/MIB1, p53, bcl-2, c-erbB-2, E cadherin, CD44v, CD31, oestrogen and progesterone receptors' (ER, PR) antigenic sites and pS2. The exact role, if any, of VLA2 in tumour cell dissemination remains to be elucidated and the clinical relevance of VLA2 immunodetection in breast carcinomas requires further investigation of the correlation between VLA2 immunocytochemical expression and patients' outcome and response to chemotherapy.
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PMID:VLA2 integrin expression in breast carcinomas evaluated by automated and quantitative immunohistochemistry. 964 45

A 69-year-old woman was admitted to Hokuso Shiroi Hospital because of recurrent pain in the lower right side of the abdomen. Small-intestinal cancer was strongly suspected after fluoroscopy of the small intestine. Laparotomy showed advanced cancer of the ileum, of complete annular constrictive type, 9.5 x 5cm in size. Histologically it was moderately differentiated tubular adenocarcinoma. Neither visceral nor nodal metastases were found, and the patient has been well for the 20 months since surgery. The strong resemblance between the epidemiological characteristics of small-intestinal cancers and colorectal cancers prompted us to investigate the carcinogenetic mechanisms at the molecular level. A point mutation at codon 12 of the K-ras gene was found, while no alterations were noted in the p53 gene, whose mutations are frequent in colon cancers. The carcinogenetic mechanisms of the small-intestinal cancer we experienced may thus differ from those of colon cancers.
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PMID:Primary cancer of the small intestine and mutational analysis of the K-ras and p53 genes. 965 20

Cell cycle deregulation can occur at different levels in cancer. In human breast cancer it includes overexpression of cyclins D1 and E, down-regulation of cyclin-dependent kinase inhibitors and inactivation of the retinoblastoma and p53 tumor suppressor proteins. Telomerase activity is strongly associated with an immortal phenotype and expression of telomerase is linked to the cell cycle. We have recently demonstrated a connection between specific cell cycle defects within the pRB pathway and levels of telomerase activity in breast cancer. In the present study, 106 tumors were investigated for p53 gene and protein status. By single strand conformation polymorphism (SSCP) analysis, 15% showed mutations within exons 5-8 and by immunohistochemistry (IHC), 29% were p53 positive. Tumors with a telomerase activity above median (i.e., telomerase(high)) were significantly associated with p53 protein accumulation (p = 0.004), but not with p53 gene mutations. The strongest telomerase expression was found in tumors with p53 protein accumulation. Morphologic grade, estrogen and progesterone receptor expression differed significantly between the telomerase(high) and telomerase(low) groups (p < 0.0001, p = 0.016 and p = 0.046, respectively), but no difference was observed for stage or nodal status. Telomerase(high) tumors were significantly associated with a poor prognosis for node-negative (N0) patients (p = 0.008), but not for node-positive (N+) patients, whereas the opposite was demonstrated for tumors with p53 accumulation. The survival data indicated that telomerase expression has biological importance particularly for N0 tumors, suggesting that telomerase(low) tumors constitute a group of "pre-immortalized" tumors with a good prognosis.
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PMID:Telomerase activity in relation to p53 status and clinico-pathological parameters in breast cancer. 969 24

Gastric low-grade mucosa-associated lymphoid tissue (MALT) lymphoma is a unique disease. A vast majority of lymphoma cells are centrocyte-like cells or resemble monocytoid B cells, and occasionally show plasmacytic differentiation. Immunophenotypical and immunogenotypical examinations have indicated that they are in the differentiation stage of memory B cells, whose normal counterparts are marginal zone lymphocytes or monocytoid B cells in the lymphoid tissues. It arises from chronic gastritis closely associated with Helicobacter pylori (H. pylori) infection. Mucosa-associated lymphoid tissue lymphomas of other organs are also based on acquired MALT associated with chronic inflammation or autoimmune diseases. Interestingly, the majority of gastric low-grade MALT lymphomas regress by the eradication of H. pylori. The lymphoma cells, however, are not derived from B cells reacting with H. pylori itself but from autoreactive B cells. Although the mechanism of their oncogenesis has not been clarified, previous data suggest that autoreactive B cells proliferate in response to H. pylori-specific T cells, presumably with some cytokines. The genetic instability of such B cells then induces chromosomal abnormalities including trisomy 3 and/or other genetic changes. These B cells have the ability of autonomic proliferation and, even so, they might be sensitive to T cell stimuli. Low-grade gastric lymphomas occasionally progress to high-grade malignancy. The high-grade component of MALT lymphomas are composed of large-sized lymphoma cells that are morphologically indistinguishable from nodal large B cell lymphomas. This high-grade transformation is associated with p53 abnormalities or Bcl-6 overexpression. Gastric MALT lymphoma may provide a useful model in understanding multistep lymphomagenesis.
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PMID:Gastric low-grade mucosa-associated lymphoid tissue lymphomas: their histogenesis and high-grade transformation. 970 38

The aim of this study was to investigate the expression of p53 and bcl2 proteins in a series of 107 non-small cell lung cancers (NSCLC), and to relate such protein expression to neovascularisation and the expression of vascular endothelial growth factor (VEGF). Moreover, we analysed the prognostic impact of these biological parameters on overall survival, both in univariate and multivariate analyses. An inverse association was found between bcl2 expression and microvessel count (MVC; P = 0.0004) and bcl2 and VEGF (P = 0.007). In contrast, a significant association was found between p53 expression and MVC (P = 0.03) and p53 and VEGF expression (P = 0.04). In univariate analysis, nodal status (P < 0.000001), MVC (P < 0.000001), bcl2 (P = 0.002), p53 (P = 0.03) and VEGF expression (P < 0.000001) significantly affected overall survival, but in multivariate analysis only MVC and VEGF expression retained their prognostic influence. Our results suggest that bcl2 and p53 possibly control the development of tumour angiogenesis in NSCLC, with putative mediation by VEGF. Moreover, the important influence of angiogenesis in the progression of NSCLC is further highlighted.
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PMID:Bcl2 and p53 regulate vascular endothelial growth factor (VEGF)-mediated angiogenesis in non-small cell lung carcinoma. 971 80

Expression of vascular cell adhesion molecules (VCAM) in tumors is associated with endothelial cell activation and may facilitate adherence of carcinomatous cells to the vessel wall, promoting bloodborne metastases. Expression of VCAM was investigated in 202 breast carcinomas using automated (Ventana System) and quantitative (SAMBA image analyzer) immunoperoxidase staining of frozen sections. Positive VCAM immunoreactivity was observed in 83 tumors (41%) (mean immunostained surface, 12.4%; SD, 10.5). The mean area of immunostaining was correlated with clinical and pathologic prognostic indicators and with the immunohistochemical expression in tissue sections of various indicators of cell proliferation, metastatic potential, and drug resistance or sensitivity, evaluated according to the same method. There was no correlation of VCAM immunoreactivity with tumor size, type, or grade or with nodal status. Also, no significant correlation was observed between VCAM and MIB1/Ki67, p53, Bcl-2, E cadherin, CD44v, cathepsin D, CD31, P-gp, ER, PR, or pS2. However, VCAM immunoreactivity was significantly correlated with ELAM and VLA2 (P = .001) and VLAs (P = .008) expression. The results suggest that VCAM expression in breast carcinoma tissue sections is likely not a prognostic indicator. Its practical clinical relevance, if any, must be established by correlation with patients' outcomes and tumor sensitivity to drugs.
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PMID:VCAM (IGSF) adhesion molecule expression in breast carcinomas detected by automated and quantitative immunocytochemical assays. 974 2

Breast cancer is a polymorphic disease and, until now, nodal invasion and steroid receptor levels remain the most powerful and widely used prognostic indicators. Molecular oncology has proven the importance of somatic genetic events in cancer genesis and evolution. In breast cancer a number of genetic aberrations have been proposed to bear impact on disease outcome. Greatest significance has been associated to ERBB2 amplification and overexpression. More recently p53 mutations have been suggested to bear meaning in terms of cancer evolution. We discuss here the molecular epidemiology of p53 mutations in human breast tumors and the clinico-pathological significance that can be associated to them.
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PMID:p53 mutations in breast cancer: incidence and relations to tumor aggressiveness and evolution of the disease. 976 53


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