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)

In spite of the prevalence of prostatic adenocarcinoma, the development and natural history of this malignancy is poorly understood. This paper reviews the current knowledge of biomarker expression during the development and progression of prostatic adenocarcinoma. Emphasis is placed on the comparison of biomarker expression in benign prostatic epithelium, intraepithelial neoplasia (PIN), a putative preinvasive lesion, and prostatic adenocarcinoma. Within the benign epithelium, the proliferative potential is restricted to the basal cells as demonstrated by the expression of proliferating cellular nuclear antigen (PCNA). The strong expression of the bcl-2 protein, an inhibitor of a apoptosis, supports the concept that the basal cells or a subpopulation of the basal cells represent the stem cell of the epithelium. In addition, the strong expression of growth factor receptors such as the epidermal growth factor receptor (EGFr), p185erbB-2, p180erbB-3, and c-met suggests that the growth of the basal cells is regulated by autocrine or paracrine factors. The luminal cells express secretory products such as prostate specific antigen and prostatic acid phosphatase, but demonstrate little expression of PCNA as well as growth factor receptors and proto-oncogene products. These observations are consistent with the theory that the luminal cell population is derived from the differentiation of the basal cells. In contrast to the normal epithelium, PCNA expression is frequently detected in the dysplastic luminal cells of the PIN lesion. Likewise, strong expression of p185erbB-2, p180erbB-3 and the c-met proto-oncogene product is also detected in the luminal cells of PIN lesions. Other factors which are strongly expressed by the dysplastic luminal cells include the nm23-H1 gene product, tumor associated glycoprotein-72 (TAG-72), fatty acid synthetase (FASE) and proteolytic enzymes. These findings suggest that PIN lesions are derived from an impairment of the differentiation of basal cells. The majority of biomarkers such as PCNA, p185erbB-2, P180erbB-3, TAG-72, nm23-H1 and FASE which are strongly expressed in PIN lesions are also expressed in prostatic adenocarcinoma supporting the concept that PIN is a preinvasive lesion. Mutations of the p53 tumor suppressor gene, as well as strong expression of transforming growth factor alpha and bcl-2 typically occur in advanced stage prostatic adenocarcinomas and therefore likely represent late events in the development of prostatic adenocarcinoma.
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PMID:Changes in biomarker expression in the development of prostatic adenocarcinoma. 915 21

A role of genetic alterations in the p53 tumor suppressor gene has been implicated in many types of human malignancies. In this study, we examined the prevalence of immunohistochemically detectable p53 accumulation in prostatic tissues obtained from patients with prostatic adenocarcinoma, benign prostate hyperplasia and prostatic intraepithelial neoplasms. Six of 36 (16.7%) cancer cases and 2 of 11 (18.2%) cases of high-grade prostatic intraepithelial neoplasms showed p53 expression while no nuclear staining was observed in normal and hyperplastic prostatic tissues. Correlation of p53 expression with cancer stage, Gleason score and serum prostate-specific antigen level demonstrated that there was no statistically significant relationship between p53 expression and these clinicopathological parameters. Also, no significant association between p53 expression and prognosis was observed.
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PMID:Immunohistochemical determination of p53 protein in prostatic cancer and prostatic intraepithelial neoplasms. 925 17

A case of prostatic carcinosarcoma is presented with histopathologic and immunohistochemical characteristics. A 70-year-old man presented with a history of anti-androgen (cyproterone acetate) therapy for prostatic adenocarcinoma. Diffuse and strong staining for progesterone receptor was observed in the carcinosarcoma specimen although it was completely negative in the previous adenocarcinoma specimen. It may be speculated that hormonal therapy might have facilitated the selection of a progesterone-dependent subclone of tumor cells with the ability of mesenchymal differentiation and that genetic instability due to p53 inactivation might have played a role in this process.
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PMID:Carcinosarcoma of the prostate. A case report and a possible evidence on the role of hormonal therapy. 931 26

The widespread use of prostate-specific antigen (PSA) has revealed that radiation therapy cures adenocarcinoma of the prostate less frequently than previously believed. Biologic factors (such as the complex nature of this disease) and technical factors (geographic miss, inadequate dose to the tumor volume) affect the ability of radiation to effectively treat all patients with prostate cancer. To improve treatment outcome, patients with virulent forms of the disease must be identified. The use of prognostic markers (PSA, prostate-specific membrane antigen, prostate-specific antigen doubling time) and genetic markers (12 lipoxygenase, p53, bcl-2, ploidy) may aid in the development of treatments for these patients. Technical modifications have been made to increase the total dose delivered to the prostate and the accuracy of dose delivery. Brachytherapy, proton therapy and conformal radiation therapy have been used to increase the relative integral dose. Improved prostate targeting may be achieved with the use of fiducial markers, on-line portal imaging, and endorectal magnetic resonance imaging. High linear energy transfer radiation, radiosensitizers and altered fractionation have been used in an attempt to increase the biologic equivalent dose to the tumor. Lastly, hormonal therapy and chemotherapy have been shown to decrease tumor burden and improve local control. All of these methods may improve outcome in patients with adenocarcinoma of the prostate. However, further work must be completed to translate these methods into standards of care.
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PMID:A rational approach to the treatment of prostate cancer with radiation therapy: lessons for the future. 942 69

Mutational alterations involving the p53 and retinoblastoma (RB) tumor suppressor genes are implicated in the oncogenesis of a variety of tumors. Their role in the pathogenesis of prostatic adenocarcinoma remains to be fully elucidated, and their detection in high-grade prostatic intraepithelial neoplasia (HG-PIN) has not been closely examined. We studied the immunohistochemical expression of RB and p53 proteins in HG-PIN, benign prostate, and prostatic adenocarcinoma from 25 radical prostatectomy specimens. Formalin-fixed, paraffin-embedded tissue sections pretreated with antigen retrieval in citrate buffer were stained with anti-RB antibody RB-WL-1 and anti-p53 antibody DO-7. RB immunoreactivity was present in all of the cases in the foci of HG-PIN, benign prostate, and prostatic adenocarcinoma. Mutant p53 protein was detected in 56% of HG-PIN, 72% of prostatic adenocarcinomas, and 20% of benign prostatic glands. A multivariate analysis of variance showed an overall difference in p53 immunoreactivity between HG-PIN, benign prostate, and prostatic adenocarcinoma (P < .001). There was a statistically significant difference between immunoreactivity of the benign prostate and of HG-PIN (P < .001) and between the immunoreactivity of benign prostate and prostatic adenocarcinoma (P < .001). The immunoreactivities of HG-PIN and prostatic adenocarcinoma were not statistically different (P = .3). These data suggest that RB loss might not play a role in initiation of all cases of prostatic adenocarcinoma. The p53 immunoreactivity in HG-PIN was significantly different from that found in benign prostate and was similar to that of prostatic adenocarcinoma. This is in keeping with the putative premalignant character of HG-PIN.
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PMID:Immunohistochemical expression of retinoblastoma and p53 tumor suppressor genes in prostatic intraepithelial neoplasia: comparison with prostatic adenocarcinoma and benign prostate. 952 70

Prostatic adenocarcinoma is emerging as a major cause of morbidity and mortality in the male population in the western world. Programmed cell death (apoptosis) in the prostate is activated by hormone ablation and is under the control of several regulating genes including the tumour suppressor gene p53 and the proto-oncogene bcl-2. Bcl-2 belongs to a rapidly expanding family of genes which form two functionally antagonistic groups controlling cell death and survival. Apoptosis regulating genes appear to play an important role in the development and progression of prostatic adenocarcinoma and offer a potential target for future therapeutic strategies.
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PMID:Apoptosis regulating genes in prostate cancer (review). 953 52

Current dilemmas for physicians managing patients with localized prostate cancer include deciding: (1) which patients need aggressive treatment; (2) what treatment options are best for a given patient; and (3) what treatment outcomes can be expected. This article reviews our ability to prognosticate outcome (including pathological stage and disease-free survival rate) in patients with clinically localized adenocarcinoma of the prostate (AJCC, stage T1-T2. N0, M0) subsequent to analysis of several contemporary series involving patients treated with radical prostatectomy and external-beam radiation therapy. Pretherapy prostate-specific antigen (PSA) level (< or =4 ng/mL or >20 ng/mL) and Gleason score (< or =4 or > or =8) as individual variables provide independent prognostic information for only a subset of patients undergoing radical prostatectomy and external-beam radiation therapy. Pathological stage is the most powerful predictor of outcome following radical prostatectomy, and its prediction (organ-confined vs. seminal vesicle or lymph node involvement) is aided by knowledge of clinical stage, Gleason score, and PSA level. Planned systematic biopsies also provide useful prognostic information for the prediction of pathological stage and tumor volume, as well as providing additional tissue for pathological assessment of tumor heterogeneity. Several novel markers of biological aggressiveness are associated with critical steps of the metastatic cascade (growth, invasion, angiogenesis, and resistance to apoptosis) and include the p53 tumor suppressor gene, the bcl-2 proto-oncogene, markers of increased proliferation (Ki-67), apoptosis, and angiogenesis (microvessel density). Their evaluation in clinical specimens is currently being used to prognosticate outcome. Current clinical and pathological parameters provide a "ballpark" estimate of outcome for patients with clinically localized prostate cancer. Further elucidation of the critical molecular events associated with prostate cancer progression and metastasis should help in identifying molecular markers that more accurately predict the prognosis for an individual patient with clinically localized prostate cancer.
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PMID:Prognostic markers in clinically localized prostate cancer. 956 75

Often the diagnosis of pancreas cancer needs to be established from limited cytology specimens or small biopsies. Most ductal adenocarcinomas are histologically well to moderately differentiated and mimicked closely by pancreatitis, and therefore the microscopic diagnosis can be difficult. In addition, there appears to be significant heterogeneity in the outcome of the patients with pancreatic cancer, which cannot be predicted accurately by current prognosticators such as the grade and stage of the tumor. Therefore, there is need for methods that can be used as adjuncts to routine diagnostic and prognostic parameters. This study was designed to test the utility of the fluorescent in situ hybridization (FISH) method in identifying the molecular alterations, particularly the ones that have been detected with relatively high frequency in pancreas cancer. Formalin-fixed and paraffin-embedded tissues of 10 cases were enumerated for chromosome 7, 8, 17, 18, and 20 copy numbers by using alpha-satellite probes, and for c-myc by using a gene-specific probe. The number of signals per nucleus (reflecting chromosomal copy number and status of c-myc amplification) were counted in more than two areas containing 50-500 cells. Because of tumor heterogeneity, monosomy (loss of one chromosome copy) was defined arbitrarily as one signal in >25% of nuclei. C-myc amplification was defined as more than two gene copies in >20% of the cells. The most frequent signal losses were found in chromosomes 8 (four of 10 cases) and chromosome 17 (four of 10), followed by 20 (three of 10) and 18 (two of 10). No loss of chromosome 7 was detected. In contrast, gains in chromosome copy number were identified in only one of 10 tumors, which showed gain of both chromosome 7 and 18. Amplification of c-myc gene was detected in two of 10 cases, but neither of the two had aneuploidy for chromosome 8, where the c-myc gene is located. In addition, loss in c-myc signal was observed in one case that also showed loss of chromosome 8 copy number. FISH can be used to detect chromosomal changes in pancreatic cancer; abundance of lytic enzymes in this organ is not an impediment for the applicability of this technique. Therefore it can potentially be used in the future as an adjunct to the conventional diagnostic and prognostic markers. This study confirms that loss of chromosomes, particularly chromosomes 17 and 18, which carry the p53 and DCC genes, are common in pancreas cancer. Chromosome 20 is also frequently lost. In addition, in this study, alterations of chromosome 8, which is seen commonly in prostatic adenocarcinoma but has not been previously documented in pancreatic cancer, also was detected in five of 10 tumors. Furthermore, amplification of the c-myc gene, which is located in chromosome 8, was found in the two of the remaining five cases. Further studies are needed to confirm this high incidence of chromosome 8 and c-myc alterations and their possible role in the pathogenesis of pancreatic adenocarcinoma.
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PMID:Utility of fluorescence in situ hybridization in pancreatic ductal adenocarcinoma. 1009 Apr 7

Prostate cancer is the most frequent malignancy and the second leading cause of cancer deaths among males in the Western world. The clinical course of the disease is highly complex, and genetic factors underlying tumorigenesis are poorly understood. The challenge that lies ahead is to identify the important gene(s) that causes adenocarcinoma of the prostate. Chromosomal findings by cytogenetic and molecular methods, including Southern blotting, microsatellite analysis, fluorescence in situ hybridization, and comparative genomic hybridization, revealed a high frequency of chromosomal aberrations of heterogeneous nature, including: -1, +1, -1q, +4, -6q, -7, +7, -8, -8p, -8q, +i(8q), -9, -9p, -10, +10, +11, -12, -13q, -16, -16q, +16, -17, +17, +17q, -18, +18, -18q, +19p, +20q, +X, -Xq, -Y, and +Y. Specific chromosomal regions of alterations were 1q24-25, 2cen-q31, 5cen-q23.3, 6q14-23.2, 7q22-q31, 8p12-21, 8p22, 8q24-qter, 10q22.1, 10q23-25, 11p11.2, 16q24, 17p13.1, 18q12.2, and Xq11-12. Recently, a predisposing gene for early onset has been localized on 1q42.2-43. The losses of heterozygosity at specific chromosomal loci from chromosomes 5q, 6q, 7q, 8p, 8q, 10q, 13q, 16q, 17p, 17q, and 18q are generally correlated with poor prognosis in advanced tumor stage. In addition, an abnormal function of known tumor suppressor genes from these regions have been observed in prostate cancer. Although, the amplification of the androgen receptor gene at Xq11-13 and HER-2/neu gene at 17q11.2-q12 are novel findings, no single gene has been implicated in harboring prostate cancer. Frequent inactivation of PTEN/MMAC1 tumor suppressor gene at 10q23, MXI-1 at 10q25, KAI-1 at 11p11.2, Rb at 13q14.2, and p53 at 17p13.1 and deregulation of c-myc oncogene at 8q24 have recently been the subject of intense scrutiny and debate.
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PMID:Chromosomal basis of adenocarcinoma of the prostate. 1043 55

Morphologic features alone can usually be used to distinguish prostatic adenocarcinoma and urothelial carcinoma of the urinary bladder. Poorly differentiated tumors, however, can occasionally have features of both neoplasms, making determination of site of origin difficult. No study has provided a panel of antibodies to assist in the distinction of these two tumors. For this study, 73 examples of moderately and poorly differentiated prostatic adenocarcinoma and 46 examples of high-grade urothelial carcinoma were obtained from radical resection specimens. Immunohistochemical studies were performed using the following panel of antibodies: cytokeratin (CK) 7, CK 20, 34betaE12, Leu M1, carcinoembryonic antigen (CEA)m, CEAp, p53, Leu 7, prostate-specific acid phosphatase (PSAP), prostate-specific antigen (PSA), and B72.3. Mucicarmine was also performed. Intermediate and high-grade prostatic carcinoma were compared and then high-grade prostatic carcinoma was compared with high-grade urothelial carcinoma. PSA and PSAP each stained 94% of prostatic adenocarcinomas, but no urothelial carcinomas. Leu 7 stained 94% of prostate and 17% of urothelial carcinomas. Over half of the urothelial carcinomas showed positivity for 34betaE12 (65%), as did two cases of prostatic carcinoma (6%). Eighty-three percent of urothelial carcinomas and 12% of prostatic adenocarcinomas stained with CK 7. Forty-one percent of urothelial carcinomas and 12% of prostatic carcinomas were reactive for CEAm, and p53 stained 33% and 3% of urothelial and prostatic adenocarcinomas, respectively. No significant difference was seen in the expression of CEAp, CK 20, B72.3, Leu M1, or mucicarmine between prostate and urothelial carcinoma. We propose a panel of six antibodies to assist in the distinction of high-grade prostatic adenocarcinoma from high grade urothelial carcinoma: PSA, PSAP, 34betaE12, Leu 7, CK 7, and p53. The first three antibodies should be used initially; if results are negative, the remaining antibodies may be employed.
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PMID:Immunophenotype of high-grade prostatic adenocarcinoma and urothelial carcinoma. 1110 75


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