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)

Seventy-three cases of malignant, atypical, and multicentric granular cell tumors of soft tissue were studied to clarify criteria for malignancy and prognostic factors. Six histologic criteria were assessed: necrosis, spindling, vesicular nuclei with large nucleoli, increased mitotic activity (> 2 mitoses/10 high-power fields at 200x magnification), high nuclear to cytoplasmic (N:C) ratio, and pleomorphism. Neoplasms that met three or more of these criteria were classified as histologically malignant; those that met one or two criteria were classified as atypical; and those that displayed only focal pleomorphism but fulfilled none of the other criteria were classified as benign. Hence, 46 cases were classified as histologically malignant, 21 as atypical (3 were multicentric), and 6 as benign (all were multicentric). The patients with benign multicentric and atypical granular cell tumors had no metastases and there were no tumor deaths. In contrast, 11 of 28 patients (39%) with malignant granular cell tumor with follow-up information died of disease at a median interval of 3 years; 8 of 28 (29%) were alive with disease, and 9/28 (32%) were disease free (median intervals, 2 and 7 years, respectively). There were local recurrences in 9 of 28 malignant cases (32%) and metastases in 14 of 28 (50%) (median intervals, each 2 years). Forty-eight cases were studied immunohistochemically; 100% expressed vimentin, 98% S-100 protein, 98% neuron-specific enolase, 69% CD57, and 65% CD68. Alpha-smooth muscle actin, desmin, epithelial membrane antigen (EMA), cytokeratins (with CAM 5.2 and KL-1), chromogranin, and HMB45 were not detected. The proliferative index with Ki67 (MIB 1) was 10-50% in 14 of 25 malignant tumors (56%), and immunostaining for p53 was detected in 50% or more of tumor cells in 17 of 25 (68%); both of these factors were statistically significant with regard to the histologic classification as benign, atypical, or malignant. Ultrastructural examination of 13 benign, atypical, and malignant granular cell tumors showed engorgement of the cytoplasm with complex granules and lysosomes, as well as Schwannian features. By flow cytometric DNA analysis, two of six malignant tumors were aneuploid, two were hyperdiploid, and two were diploid. One atypical tumor was aneuploid and all 11 benign tumors were either diploid (9 cases) or hyperdiploid (2 cases). Statistically significant adverse prognostic factors with regard to survival included local recurrence, metastasis, larger tumor size, older patient age, histologic classification as malignant, presence of necrosis, increased mitotic activity, spindling of tumor cells, vesicular nuclei with large nucleoli, and Ki67 values greater [corrected] than 10%. This study defines clinical and morphologic criteria for malignancy in granular cell tumors and shows that malignant granular cell tumor is a high-grade sarcoma with a high rate of metastases and a short survival.
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PMID:Malignant granular cell tumor of soft tissue: diagnostic criteria and clinicopathologic correlation. 966 41

Controversy continues regarding the prognostic utility of detection of p53 gene abnormalities in node-negative breast cancer. To resolve this, we used a rapid and nonisotopic PCR-single strand conformation polymorphism method to screen for mutations in exons 4-8 of the p53 gene in primary tumors from 422 node-negative breast cancer patients. The prevalence of p53 mutation in the exons tested was 18%. p53 mutation was significantly associated with several markers of poor prognosis including larger tumor size, high tumor grade, low hormone receptor content, increased expression of MIB-1 (Ki-67), amplification of the HER-2/neu oncogene, and accumulation of the p53 protein. After a median duration follow-up period of 74 months, the parameters of tumor diameter > or =20 mm, HER-2/neu oncogene amplification, and p53 mutation were found to be associated with a statistically significant shortened duration of disease-free and overall survival, but not the parameters of tumor grade, hormone receptor levels, or p53 expression. The poor prognosis associated with p53 mutation was observed primarily in patients with a tumor diameter of > or =20 mm. In multivariate analysis, p53 mutation was a risk factor for increased risk of recurrence and death from breast cancer independent of tumor size, hormone receptor levels, HER-2/neu amplification, and MIB-1 expression. We conclude that a relatively simple and rapid single strand conformation polymorphism method of determining p53 mutation status in node-negative breast cancers can provide independent prognostic information.
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PMID:Analysis of p53 gene mutation by polymerase chain reaction-single strand conformation polymorphism provides independent prognostic information in node-negative breast cancer. 967 32

The so-called nasal gliomas (nasal cerebral heterotopias) are rare, congenital, benign masses of neurogenic origin with intra or extranasal location, or both. An intranasal case is reported in a 7-month-old infant who successfully underwent surgery with the intranasal approach. The tumor had no intracranial extension and the child is free of disease after a three-year follow-up. Immunohistochemical study confirmed the glial (GFAP+) and neuronal (NSE+) nature of the cells composing the mass. In addition to the clinical behavior, the benign nature of the tumor is also indicated by the negativity of Ki67 (MIB-1) and p53 proliferation markers as well as by CD44 negativity. As far as we know, this is the first reported case of nasal glioma subjected to immunohistochemical investigation of proliferation activity.
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PMID:So-called nasal glioma: case report with immunohistochemical study. 967 25

Twenty-six specimens of tubular adenoma and 7 specimens of adenocarcinoma in adenoma of the colon were examined to evaluate apoptosis between adenoma and early adenocarcinoma. Cell proliferation and cell death seemed to be balanced in adenoma with mild and moderate atypia, but unbalanced in adenoma with severe atypia and cancer. Apoptosis was considered to be suppressed at cancer in some cases. However, a number of apoptosis increased at cancer in other cases. Necrosis was seen only in cancer areas. The ratio of cells simultaneously stained by anti-Ki-67 antibody (MIB-1) and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-nick end labeling (TUNEL) tended to be high from adenoma with moderate atypia to cancer, suggesting the unstableness of DNA. It is possible that cancer cells having highly unstable DNA easily underwent apoptosis as well as necrosis, accidentally. The p53 protein was positive only in cancer areas of three cases. One of these three showed decreased apoptosis in a cancer area, but the other two cases showed increased apoptosis. Furthermore, certain numbers of cancer cells were double-stained by p53 immunohistochemistry and TUNEL. These results suggest that the p53 protein may contribute to suppress apoptosis in the last stage of carcinogenesis of the colonic adenocarcinoma, but other factors including extrinsic stimulation may cause apoptosis despite the mutation of p53 protein.
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PMID:Apoptosis in adenoma and early adenocarcinoma of the colon. 969 Jan 32

The biologic behavior of gastrointestinal stromal tumors is difficult to predict, and they can be best studied in a site-specific fashion. The aims of this study are to analyze the clinicopathologic parameters and assess the prognostic value of p53 (DO-7) and Ki-67 (MIB-1) immunoreactivities in small intestinal stromal tumors (SIST). The histopathologic features of 31 SIST were assessed and categorized into two groups as follows. Group A (clinically aggressive) in which death due to tumor, metastasis, recurrence or relapsed melena were seen (n = 15) and group B (clinically benign; n = 16). For both groups, the period of follow-up was 30-144 months. p53 overexpression was observed in four tumors (31%) in group A, and in none in group B. For groups A and B, the mean Ki-67 index was 16.8 +/- 12.5 and 8.4 +/- 12.6, respectively. Statistical analysis revealed that the significant predictors of malignancy were high cellularity (odds ratio (OR) = 999; 95% confidence interval (CI) = 0-999); p53 overexpression (OR = 999; CI = 0-999); size of tumor > or = 5 cm (OR = 18.0; CI = 1.9-171.9); > or = 5 mitoses/50 high-power fields (HPF) (OR = 17.1; CI = 1.8-165.9); pleomorphism (OR = 17.1; CI = 1.8-165.9); and necrosis (OR = 11.9; CI = 2.2-65.1; P < 0.05). High Ki-67 index (> or = 8.4) had a marginal impact on risk (OR = 4.1; CI = 0.8-20.2; P = 0.08). In conclusion, high cellularity, p53 overexpression, size of tumor > or = 5 cm, > or = 5 mitoses/50 HPF, pleomorphism and necrosis are important parameters for the prediction of malignancy in SIST.
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PMID:Small intestinal stromal tumors: a clinicopathologic study of 31 tumors. 970 40

The incidence of primary lymphomas of the central nervous system (CNS) has significantly increased over the last years. However, the pathogenesis of this serious and fatal disease is still largely unknown. The aim of the present study was to investigate whether impairment of apoptosis is involved in the pathogenesis of primary CNS lymphomas. A series of 35 primary CNS lymphomas was investigated for the presence of apoptotic cells and the expression of apoptosis-inhibiting and proapoptotic gene products of the bcl family by application of the terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling (TUNEL) technique and immunohistochemistry. The majority (23/35) of the tumors contained no or less than 10% of apoptotic cells. All tumors were MIB-1 positive, and 53% of them showed a high proliferative activity with more than 20% MIB-1-positive cells. The bcl-2 gene was expressed in 54% of the tumors (19/35), whereas bcl-x and bax gene products were present in only a low fraction of these lymphomas (4/35). In contrast, bak and the tumor suppressor gene p53 product were not detectable. These findings indicate that apoptosis is inhibited in the majority of this series of primary CNS lymphomas. Since there was no statistical correlation between the degree of apoptosis and the expression of proteins of the bcl gene family, other apoptosis-inhibiting factors may be involved in the pathogenesis of primary CNS lymphomas.
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PMID:Apoptosis and apoptosis-related gene products in primary non-Hodgkin's lymphoma of the central nervous system. 970 31

Three cases of primary gliosarcoma (GS) were studied by immunohistochemical, ultrastructural and fluorescence in situ hybridization (FISH) methods. All tumors occurred in the supratentorial regions of the body. No patient had a prior history of irradiation to the brain. All patients died of tumor within 1 year, and autopsies were performed in two cases. Microscopically, each of the three tumors showed a mixture of glioblastoma (GBM) and a sarcomatous component (SC), which resembled fibrosarcoma with various histological features. Numerous collagen and reticulin fibers were seen in the SC of all tumors. Glial fibrillary acidic protein (GFAP) was immunoreactive only in the gliomatous component (GC). Factor VIII-related antigen was negative except for endothelial cells. One tumor exhibited alpha-smooth muscle actin positivity in the SC. Expression of MIB-1 and p53 protein was demonstrated in both components for all tumors. Labeling indices (LI) for MIB-1 ranged from 7.7 to 36.1%, and LI for p53 protein ranged from 2.9 to 57.0%. Ultrastructurally, astrocytic cells were characterized by a polygonal configuration with many cytoplasmic projections and occasional filaments. Spindle-shaped fibroblasts in the SC contained well-developed rough endoplasmic reticulum. Fluorescence in situ hybridization (FISH) performed on fresh materials or paraffin-embedded tissue demonstrated single signals for chromosome 10 in 40.6-58.3% of cells and for chromosome 17 in 37.9-48.6% of cells. Two tumors were regarded as containing losses of both chromosomes 10 and 17, while the third showed a substantial loss only of chromosome 10. As similar aberrations have been reported in GBM, these chromosomal abnormalities suggest a common pathogenesis in GS and GBM.
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PMID:Gliosarcoma: an immunohistochemical, ultrastructural and fluorescence in situ hybridization study. 973 6

Gliofibromas are rarely encountered astrocytic tumours comprising of astrocytic and benign fibroblastic components. They commonly occur in first two decades of life. However, the exact behaviour is not fully known and their histogenesis is also still debatable. We report three cases of gliofibroma in which we studied proliferative markers (MIB-1) and p53 protein expression. In these tumours, occurrence in adult life is in contrast to that reported in the literature. Depending upon the morphology and proliferative Labelling Index we classified these tumours into low grade (benign) and high grade (malignant/anaplastic).
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PMID:Gliofibroma: mixed glial and mesenchymal tumour. Report of three cases. 974 6

Conventional histopathological criteria based on light microscopy are used in pulmonary oncologic pathology in order to establish the diagnosis of tumor, but most frequently they are insufficient, accurate diagnosis requiring ultrastructural and immunohistochemical investigations. The method of immunostaining allowed some molecular marker to be evaluated. Some of them seem to be important in carcinogenesis as a general process, while others have high specificity for lung tumors. Estimation of EGFR and c-erbB-2 protein immunoreactivity showed a significantly stronger staining with NSCLC and was correlated to the poor differentiation of the tumors, undergoing an aggressive biological behavior and an unfavorable prognosis. The expression of p53 protein was found in 19 cases by immunostaining with DO-7 antibody. Immunotracing of more than 50% of the tumoral cells was a predictive factor for the progression of the disease. The growing rate of tumoral proliferative activity was evaluated by immunotracing technique (MIB-1), allowing the Ki-67 index of labeling to be calculated.
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PMID:Immunohistochemical markers in the morphological diagnosis of lung carcinoma. 974 20

Predicting the clinical behavior of prostate carcinoma can be difficult; one approach is to identify molecular prognostic markers. We evaluated proliferative rate (MIB-1 antibody) and expression of bcl-2, p53, and retinoblastoma (pRB) proteins, which have cell cycle-related functions, in 208 consecutive radical prostatectomy specimens. Values were correlated with histopathologic parameters (Gleason tumor score, tumor amount, capsule invasion, and involvement of surgical margins, seminal vesicles, or lymph nodes) and with recurrence-free survival (4-year median follow-up). A high MIB-1 proliferative rate was associated with all of the measured histopathologic parameters, p53 overexpression with tumor amount, and pRB expression with positive lymph nodes. pRB and p53 expression levels were not associated with differences in recurrence-free survival. A high MIB-1 proliferative rate and bcl-2 positivity were associated with increased recurrence, both considered individually, and also independently and additively when examined together and with the most predictive histopathologic factors (Gleason tumor score and seminal vesicle involvement). MIB-1 proliferative rate and bcl-2 positivity may prove to be useful markers for poor prognosis in prostate carcinoma.
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PMID:Bcl-2 oncoprotein positivity and high MIB-1 (Ki-67) proliferative rate are independent predictive markers for recurrence in prostate carcinoma. 976 29


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