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 prognosis of gastric carcinoma remains unfavorable despite a greater understanding of its molecular pathology. This retrospective study of primary gastric carcinomas was collected from one of the highest risk regions of China and examined for the oncogenetic expression of p53, c-erbB-2, and PCNA using immunohistochemistry and DNA contents by flow cytometry and image analysis. These products are reported to influence the tumor behavior. The p53 nuclear and c-erbB-2 membrane-bound stainings were seen in 58% and 34% of cases, respectively. A high PCNA index was found in 90% of the tumors. The p53 expression did not correlate with the histological differentiation, gross morphology, and depth of tumor invasion. Additionally, p53 and c-erbB-2 reactivity did not correlate with the proliferative index (PI) or S-phase DNA content. However, the mutant p53 expression was detected in the dysplastic cells adjacent to the tumor, suggesting a possible role of the oncogene in tumor pathogenesis. Mutant p53 expression can also be helpful in early detection of cases with dysplasia in well-differentiated adenocarcinomas.
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PMID:Gastric carcinoma: recent issues in prognostic factors. 777 39

The biologic behavior of invasive pituitary adenomas is poorly understood and appears to be intermediate between intrasellar adenomas and pituitary carcinoma. Utilizing immunohistochemistry on tissue sections, we examined 10 invasive pituitary adenomas involving the sphenoid sinus with a panel of cellular and molecular markers and compared the results with 10 noninvasive pituitary adenomas and five normal pituitary glands. The panel included Ki-67 and PCNA (proliferation cell nuclear antigen), cell proliferation indicators; interleukin 6 (IL-6), a multifunctional cytokine; heat shock protein 27 (HSP 27), a stress response protein; and p53, a tumor suppressor gene product. We found strong expression of IL-6 in normal pituitary glands, 20% of noninvasive and 50% of invasive adenomas. HSP 27 was absent in normal glands and present in 10% of noninvasive and 50% of invasive adenomas. The Ki-67 and PCNA proliferation index was above normal but was essentially the same in the two groups. p53 was not detected in any specimens. We propose that both IL-6 and HSP 27 may be markers of biologic aggression in pituitary adenomas.
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PMID:Biologic markers of invasive pituitary adenomas involving the sphenoid sinus. 777 77

Breast carcinomas are known to express platelet-derived growth factor (PDGF), a known connective tissue mitogen. In order to further evaluate the potential role of PDGF in these epithelial tumors, expression of the PDGF B chain (PDGF-B) and the PDGF receptor beta subunit (PDGFR) was analyzed by immunocytochemistry and in situ hybridization in 49 benign and malignant breast tissues. PDGF-B expression was analyzed with respect to the expression of the proliferating cell nuclear antigen, as well as tumor grade, p53 overexpression, estrogen receptor, progesterone receptor, and c-erbB-2 expression. Expression of PDGF-B protein and mRNA was restricted to the breast epithelium and tumor cells except for scattered tissue macrophages. A strong correlation was found between increasing proliferating cell nuclear antigen indices and PDGF-B expression in both nonmalignant (P = 0.01) and malignant (P = 0.02) breast specimens. Decreased PDGF-B expression was found in postmenopausal atrophic breast tissue compared with normal breast tissue (P = 0.04). Within the subgroup of malignant tumors, no correlations were found between PDGF-B expression and tumor grade or p53 overexpression. In 16 of the malignant tumors evaluated for estrogen/progesterone receptor status and c-erbB-2 overexpression, no correlations with PDGF-B expression were found. Membranous PDGFR immunostaining was present within the fibroblastic cell population in all of the tissues examined but not in the nonmalignant breast epithelium. Six malignant specimens had detectable cytoplasmic expression of PDGFR. There was no correlation between this PDGFR expression and proliferating cell nuclear antigen indices, but a correlation was noted between increasing estrogen receptor expression and PDGFR cytoplasmic expression (P = 0.04). The results support a paracrine role for PDGF-B in malignant and benign breast epithelial cell proliferation.
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PMID:Expression of platelet-derived growth factor B-chain and the platelet-derived growth factor receptor beta subunit in human breast tissue and breast carcinoma. 778 Sep 88

Immunocytochemical methods were examined for their sensitivity in the detection of nuclear antigens (proliferating cell nuclear antigen, Ki-67 associated proliferative antigen and p53 protein) in the leukemic cells. A comparative study of the biotin streptavidin enhanced peroxidase technique, the biotin streptavidin enhanced alkaline phosphatase technique and the indirect immunoperoxidase technique showed that the indirect immunoperoxidase technique was more sensitive than the other techniques for detecting p53 protein. The results of several fixation methods demonstrated that formalin and methanol, formalin and ethanol (1:9) and buffered formalin acetone gave good results for detecting p53 protein. In the eosinophils and neutrophils the endogenous peroxidase reaction disappeared after microwave heating for over three minutes. Thus enzyme pre-blocking of blood smears could be omitted. Four solutions for microwave treatment were tested. Excellent antigen retrieval was obtained with pH6.4, pH7.4 phosphate buffer saline and pH6.0 citric acid. However, the nuclear antigens could not be retrieved and the positive reaction could not be obtained after the treatment with distilled water. The optimal microwave heating time was five to ten minutes. The indirect immunoperoxidase technique performed using microwave treatment under these optimal conditions may be potentially applicable for detecting low levels of nuclear antigens in the leukemic cells within conventional blood smears.
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PMID:[Detection of nuclear antigen within the leukemic cells using immunocytochemical technique]. 778 70

It is important to know the proliferating ability and the malignant potential of tumor tissues. We have examined the expression of PCNA/cyclin, p53 and C-erbB-2 in transitional cell carcinoma of the human urinary bladder by an immunohistochemical method, and compared the results with the histological grade, stage and survival rate. Immunohistochemical studies, using monoclonal and polyclonal antibodies, on these proteins were performed with formaline fixed-paraffin sections of tumor tissue from 40 patients with bladder cancer. Generally, a higher grade and higher stage tumors expressed PCNA/cyclin, p53 and C-erbB-2 with a greater frequency than the tumors with a lower grade and lower stage and strongly stained cases had a lower survival rate than weakly stained cases. These findings suggest that the detection of each antigen is useful for estimating the malignant potential of transitional cell carcinoma as the adjuvant studies, because of its applicability to paraffin-embedded tissue sections and its simple, rapid technique.
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PMID:[Expression of PCNA/cyclin, p53, C-erbB-2 versus histological grade in transitional cell carcinoma of urinary bladder]. 778 54

An immunohistochemical analysis with monoclonal antibodies against Ki-67 (MIB 1), PCNA (PC10), p53 and Lewis X antigen was performed on 47 squamous carcinomas of the larynx after partial laser resection. Ki-67 index and expression of Lewis X antigen correlated significantly with both tumor recurrence rate and tumor-free interval. A much weaker relationship was found for the expression of proliferating cell nuclear antigen (PCNA), and no correlation existed with p53 expression. In conclusion, examination of Ki-67 and Lewis X antigen is thought to provide useful prognostic information concerning laser-resectable squamous carcinomas of the larynx.
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PMID:[Value of monoclonal antibodies (PC 10, MIB1, p53 and LeuM 1) for assessing the prognosis of patients with squamous epithelial carcinoma of the larynx after partial laser resection]. 779 71

Histological, immunohistochemical, and flow cytometric characteristics of three unusual parotid gland tumors are described. The patients were adult white men with carcinoma ex pleomorphic adenoma, true malignant mixed tumor, and primary parotid gland chondrosarcoma. The carcinoma ex pleomorphic adenoma showed evidence of simultaneous epithelial, myoepithelial, and mesenchymal differentiation by immunohistochemistry. The true malignant mixed tumor exhibited variable positivity for two keratins, vimentin, proliferating cell nuclear antigen, Ki67, and p53. The chondrosarcoma initially stained for vimentin, S100, muscle-specific actin, proliferating cell nuclear antigen, and Ki67, but it lost actin expression in its first recurrence, accompanied by more extensive Ki67 staining. DNA ploidy varied from diploid to aneuploid with intratumoral variation in the carcinosarcoma. S-phase fractions ranged from 2.43% to 13.9%. The findings underscore the diversity of tumors that may be pathogenetically related to, and at times derived from, pleomorphic adenoma.
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PMID:Unusual mesenchymal and mixed tumors of the salivary gland. An immunohistochemical and flow cytometric analysis of three cases. 780 57

Sixty-six unselected breast cancers were analyzed in cytologic smears and histologic sections for the expression of Ki-67, proliferating cell nuclear antigen (PCNA), estrogen receptor protein (ERP), and p53 protein using a standard immunochemical method. The results, expressed as both positive cases and labelling index (LI), were compared with clinical and pathobiological variables. Ki-67 and PCNA immunostaining was seen in all cases, whereas ERP was detectable in 46/63 cases and p53 protein in 20/66 cases. The expression of these markers was generally lower in cytology than in histology, though the differences were not statistically significant. PCNA-LI and Ki-67-LI were closely correlated (P < 0.001), the mean PCNA:Ki-67 ratio being 0.92 +/- 0.57. Occasional discrepancies, however, were found. PCNA and Ki-67 expression was associated with an increase in histologic grade and a decrease in ERP content of tumors, whereas p53 was statistically associated with no clinical or pathobiological variables. The data suggest that proliferative activity and oncogene overexpression may be reliably evaluated in breast cancer by FNA cytology, though PCNA is not a suitable indicator for cell proliferation. The results do not resolve the issue as to whether immunostaining for p53 protein constitutes a dedifferentiation product of the tumor, or is a fundamental aspect of the malignant progression. Survival studies in a larger series of tumors are thus needed to elucidate this point.
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PMID:Expression of proliferating cell nuclear antigen, Ki-67 antigen, estrogen receptor protein, and tumor suppressor p53 gene in cytologic samples of breast cancer: an immunochemical study with clinical, pathobiological, and histologic correlations. 781 60

Although patients with superficial bladder cancer (Ta, T1) have a generally good prognosis, those patients who develop muscle-invasive tumours or metastatic disease at recurrence do poorly clinically. In the current study 69 patients undergoing complete transurethral resection for superficial transitional cell cancer of the bladder were investigated for different clinical and biological characteristics as possible prognostic factors: age, sex, performance of instillation therapy and immunohistochemical determination of mutational inactivation of p53 tumour-suppressor gene (monoclonal antibody PAb 1801) as well as immunohistochemical determination of the proliferation rate by staining for PCNA (proliferating cell nuclear antigen) (monoclonal antibody PC 10). After a median follow-up of 45.8 months, 12 of 14 patients (85.7%) with more than 20% of cells positive for p53 had disease progression with muscle-invasive growth compared with only one of 55 patients (1.8%) negative for p53 (P < 0.01, chi 2 test). During univariate analysis histological grade (G1 vs G2) (P = 0.0373), positivity for PCNA (> 60% of cells) (P = 0.0033) and positivity for p53 (P < 0.001) were significant prognostic factors for disease progression (log-rank test), while during multivariate analysis only positivity for p53 was a significant predictor for relapse of bladder cancer (P = 0.0029) (multivariate Cox regression analysis). The immunohistochemical detection of mutations of the p53 gene has been demonstrated to be a reliable, easily performed and thereby widely available technique for the investigation of fresh-frozen or paraffin-embedded tumour specimens. The results demonstrate the important role of the p53 tumour-suppressor gene protein in the development and for the progression of bladder cancer. If the high prognostic value of p53 mutations in superficial bladder cancer is confirmed in larger prospective trials, more aggressive therapeutic strategies could be discussed for patients with p53 mutations in their tumour specimens.
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PMID:p53 immunohistochemistry as an independent prognostic factor for superficial transitional cell carcinoma of the bladder. 781 40

Over-expression of transforming growth factor-alpha (TGF-alpha) is consistently seen in spontaneous transformants of rat liver derived epithelial cells (RLE phi 13) and has been implicated in the transformation of other cultured cells. We have constitutively over-expressed TGF-alpha in RLE phi 13 cells, which are known to express epidermal growth factor receptors, to determine if TGF-alpha over-expression plays a role in transformation or differentiation, or both, of these cells. Early passage RLE phi 13 cells were infected with a replication-defective murine retrovirus that expresses both the full length coding sequence for human TGF-alpha and the neomycin-resistance gene. Integration of the transcriptionally active provirus and expression of TGF-alpha mRNA were confirmed. Neither morphologic transformation nor molecular evidence for differentiation was noted in TGF-alpha-producing clones. However, these clones did exhibit an accelerated growth rate, increased expression of several cell cycle related genes including mitotic cyclic B1, proliferating cell nuclear antigen, c-myc, and p53 as well as increased expression of the preneoplastic marker enzyme, glutathione-S-transferase. This suggests that over-expression of TGF-alpha results in increased cell cycling, and that subsequent events must be necessary for cellular transformation or differentiation or both.
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PMID:Constitutive over-expression of transforming growth factor-alpha in rat liver epithelial cells leads to increased cell cycling without transformation. 782 Mar 13


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