Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

p53, p185erbB-2, and epidermal growth factor (EGF) receptor are well-characterized biomarkers in invasive adenocarcinoma of the breast and in ductal carcinoma in situ. erbB-2 Protein (p185erbB-2) must be identified clearly on cytoplasmic membranes while cytoplasmic expression is ignored for breast cancers to be classified as overexpressing p185erbB-2. For p53, nuclear staining and the percent positive cells are considered, but rules for "cut-offs" are not defined. Evaluation criteria for biomarkers in prostate cancer are preliminary and the "rules" may not be the same as for breast cancer. Because the initial methods of fixation and tissue processing can change both the pattern and intensity of immunohistochemical identification of specific antigens and localization of receptors may change after the receptor-ligand interactions, we evaluated the effects of fixation both on the immunolocalization and intensity of expression of p53, p185erbB-2, and EGF receptor. We also studied the patterns of p185erbB-2 and p53 expression in a series of breast cancers evaluated concomitantly with a group of prostate cancers. Our results confirm that p53 mutations are common in breast cancer and that there is strong expression of p185erbB-2 on the membranes of a subset of breast cancers. The patterns of staining for both p53 and p185erbB-2 are different in prostate and breast cancers. A much lower proportion of prostate tumors than breast tumors have more than 10% of tumor cells with detectable nuclear p53 protein, but this proportion increases markedly in metastatic tumors or in primary stage D prostate cancer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evaluation of biomarkers in breast and prostate cancer. 782 98

Eighty-five prostate cancer specimens from prostate resections were analyzed for the presence of p53 gene mutations by immunohistochemical staining for P53 protein. DNA from thirty-four of these samples was also analyzed for mutations in exons 5-8 by single-strand chain polymorphism (SSCP) analysis. One sample had P53 staining by immunohistochemistry, one sample was positive for a p53 mutation by SSCP, and one sample was positive by both techniques. Mutations in the two samples that were positive by SSCP were confirmed by nucleotide sequencing. In a separate study of ten lymph nodes that contained prostate cancer metastases, one had detectable P53 protein by immunohistochemical staining. Therefore, p53 mutations appear to be low frequency events in primary prostate cancer.
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PMID:p53 oncogene mutations in human prostate cancer specimens. 790 14

A number of genetic changes have been documented in prostate cancer, ranging from allelic loss to point mutations and changes in DNA methylation patterns (summarized in Fig 1). To date, the most consistent changes are those of allelic loss events, with the majority of tumors examined showing loss of alleles from at least one chromosomal arm. The short arm of chromosome 8, followed by the long arm of chromosome 16 appear to be the most frequent regions of loss, suggesting the presence of novel tumor suppressor genes. Deletions of one copy of the Rb and p53 genes are less frequent as are mutations of the p53 gene, and accumulating evidence suggests the presence of an additional tumor suppressor gene on chromosome 17p, which is frequently inactivated in prostate cancer. Alterations in the E-cadherin/alpha catenin mediated cell-cell adhesion mechanism appear to be present in almost half of all prostate cancers, and may be critical to the acquisition of metastatic potential of aggressive prostate cancers. Finally, altered DNA methylation patterns have been found in the majority of prostate cancers examined, suggesting widespread alterations in methylation-modulated gene expression. The presence of multiple changes in these tumors is consistent with the multistep nature of the transformation process. Finally, efforts to identify prostate cancer susceptibility loci are underway and will hopefully elucidate critical early events in prostatic carcinogenesis.
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PMID:Molecular biology of prostate cancer. 793 45

The expression of the p53 protein was studied in 10 men with prostate cancer by means of an immunohistochemical method. Strong staining for p53 was found in six of ten prostate cancer (60%, mean: 26% of malignant cells stained in the positive tumours). On the other hand, the cell nuclei in benign glands did not stain positively. Immunohistochemical pattern of p53 was not related significantly to clinicopathologic parameters in the cases examined. However, significant relationship was observed between prostate cancer stage D and stage B and mean of expression of p53 in both groups. Also, relationship between mean of expression of p53 of tumoral cells of grade IV and mean of expression of p53 of tumoral cells of grades I, II and III was observed.
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PMID:[Expression of p53 in prostatic carcinoma]. 794 81

Metastasis suppressor activities have previously been mapped to human chromosomes 17 and 11. Decreased expression of the metastasis suppressor gene NM23, which is located on chromosome 17, has been correlated with increased metastatic potential in mammary cancers. A region on human chromosome 11, from 11p11.2-p13, has been shown to suppress metastasis in rat prostatic carcinoma cells. In both cases the metastasis suppressor activity had no effect on tumorigenicity or tumor growth rate, demonstrating that the encoded activities are distinct from effects of tumor suppression. To determine whether these human chromosomes encode general or tissue-specific metastasis suppressor activities, a truncated human chromosome 17 (i.e., pter-q23) and a full-length human chromosome 11 were separately transferred into highly metastatic rat mammary and prostate cancer cell lines and tested for their ability to suppress spontaneous metastasis in vivo. These studies demonstrated that when the pter-q23 region of human chromosome 17 is retained by the microcell hybrids, the metastatic ability of both mammary and prostatic cancer cells is suppressed. In contrast, when the pter-q14 region of human chromosome 11 is retained, only the metastatic ability of prostatic cancer cells is suppressed. Additional studies demonstrated that the metastasis suppressor activity encoded by the chromosome 17 pter-q23 region is p53-independent and not due to enhanced expression of NM23 protein.
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PMID:Differential suppression of mammary and prostate cancer metastasis by human chromosomes 17 and 11. 795 74

Previous studies have demonstrated that androgen responsive human prostate cancer cells can be induced to undergo programmed cell death after androgen ablation. By contrast, androgen-independent human prostate cancer cells do not activate this apoptotic pathway in response to androgen ablation. In the present study, two androgen-independent human prostatic cell lines, PC-3 and DU-145, were used as in vitro model systems to investigate the possibility of induction of programmed cell death in response to non-androgen ablative cytotoxic drugs. Treatment of these cells with the fluorinated pyrimidines, 5-fluoro-2-deoxyuridine or trifluorothymidine, resulted in a significant decrease in cell viability, over a period of 96 hr of exposure to the drugs, as determined by the trypan blue exclusion assay. The characteristic DNA fragmentation into a nucleosomal ladder and induction of expression of specific apoptosis-related genes, such as TRPM-2/SGP-2, and TGF-beta 1, but not the growth-related genes, c-myc, c-fos, and p53, temporally correlated with activation of apoptotic cell death in both systems. Simultaneous treatment with exogenous thymidine completely abrogated the fluoropyrimidine-induced cytotoxic effect in both cell lines, as well as the nucleosomal fragmentation of DNA, indicating that this apoptotic process is due to the induction of "thymineless" state. These results suggest that androgen-independent human prostate cancer cells retain the ability to activate the apoptotic cascade, after treatment with cytotoxic drugs that induce a "thymineless" state.
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PMID:Induction of apoptosis in androgen-independent human prostate cancer cells undergoing thymineless death. 803 80

Tissue sections from 73 radical-prostatectomy specimens were studied immunohistochemically for the presence of p53 protein. In seven specimens numerous tumor cells showed a strong nuclear immunostaining. An additional 27 revealed a more discrete and focal accumulation of p53 protein. Comparison of the pathologic characteristics of the p53-negative and -positive groups showed that the presence of p53 protein closely correlated with more advanced tumor stages (p < 0.00001), with higher primary (p = 0.0004), combined (p < 0.0001) and worst (p < 0.0001) Gleason grades, and with larger total (p = 0.0001) and high-grade (p < 0.0001) tumor volumes. No staining was found in areas of benign hyperplasia or in well-differentiated tumor zones. Our results suggest that the accumulation of p53 protein to immunohistochemically detectable concentrations is not a feature of low-grade cancer. This finding implies that abnormal p53 accumulation might be involved in the process of prostatic cancer progression.
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PMID:Immunohistochemical detection of p53 protein in human prostatic cancer. 807 22

p53 gene structure and chromosome 17p alleles were studied in the three human prostate cancer cell lines, LNCaP, DU-145, and PC-3. Our laboratory has two separate culture lines of the LNCaP human prostate cancer cells. One strain, LNCaP-GW, had a mutation in one of two alleles at position 273 (arg > his). This mutation could not be detected in a second strain of LNCaP, LNCaP-ATCC. Immunohistochemical staining for P53 protein in the cell lines indicated that protein overexpression in LNCaP was heterogeneous, even in clonal isolates derived from LNCaP-GW that contained the codon 273 mutation in every cell. We also performed in vitro and in vivo growth analysis to compare the LNCaP-GW and LNCaP-ATCC cells. LNCaP-GW grew more rapidly than LNCaP-ATCC in vitro. However, LNCaP-ATCC formed tumors efficiently when inoculated into nude mice, whereas LNCaP-GW formed tumors much less efficiently. Consideration must be given to the notion that some of these p53 mutations arose during in vitro passage. We also confirmed published findings with two other human prostate cancer cell lines. In DU-145, two mutations were found in the p53 gene. A mutation at codon 274 (pro > leu) and a second mutation at codon 223 (val > phe) were present. PC-3 cells were hemizygous for chromosome 17p. The single copy of the p53 gene had a base pair deletion at codon 138 that generated a frame shift and a new in-frame stop codon at position 169.
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PMID:p53 oncogene mutations in three human prostate cancer cell lines. 810 29

Abnormalities of the TP53 gene are currently the most common genetic alterations associated with human malignancy. The study of altered patterns of p53 protein expression in primary prostate cancer has to date yielded a much lower incidence of alteration compared to bladder, colon, lung and breast cancer. However, the analysis of prostate cancer metastases has been limited. The objective of our study was to determine the prevalence of p53 nuclear accumulation in primary, metastatic and hormone refractory prostatic adenocarcinoma, and to characterize its relationship with conventional clinicopathological variables. We used 2 antibodies (mouse monoclonal PAb 1801 and rabbit polyclonal CM-1) and an immunohistochemical method in 93 paraffin embedded tumors (48 primary tumors, 29 lymph node metastases and 16 bone metastases) to assess p53 nuclear accumulation. Overall, p53 nuclear accumulation was observed in 19 tumors (20%), including 17 with PAb 1801 and CM-1 immunoreactivities, and 2 with CM-1 immunoreactivity only. The pattern of p53 immunoreactivity was heterogeneous in most tumors, with only 3 cases exhibiting homogeneous staining. Primary, lymph node and bone metastases exhibited p53 nuclear staining in 9 of 48 (19%), 2 of 29 (7%) and 8 of 16 (50%) cases, respectively (p = 0.003). In 6 of 10 primary hormone refractory tumors (60%) and in 3 of 38 primary hormone naive tumors (8%) p53 nuclear immunoreactivity was expressed (p = 0.002). P53 nuclear accumulation was significantly more common in higher grade primary tumors (p = 0.007). Our results suggest that p53 nuclear accumulation is relatively uncommon in prostate cancer. However, p53 nuclear accumulation appears to be associated with advanced stages of disease, as illustrated by its relatively higher occurrence in hormone refractory tumors and bone metastases. Furthermore, the significantly greater prevalence of p53 accumulation in bone metastases is currently the highest reported for prostate cancer.
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PMID:Immunohistochemical determination of p53 protein nuclear accumulation in prostatic adenocarcinoma. 815 73

Abnormally high levels of expression of p53 protein are found in many human cancers. In most cases increased expression is associated with point mutations in one allele of the p53 gene and loss of the other allele. Accumulation of the protein product can be detected by immunohistochemistry. p53 protein expression in 68 men with prostate cancer, followed up for at least 8 years or until death, was assessed by immunohistochemistry. The aim of the study was to determine the association between p53 protein expression, cell cycling and clinical outcome. Nine (13%) of 68 tumours stained positively for p53; all 9 tumours were category T3 or T4. p53 positive tumours had a significantly greater Gleason score than p53 negative tumours. Eight of the 9 p53 positive tumours had > 10% cells in G2 + mitosis, compared with 61% of p53 negative tumours. All 17 patients with p53 positive tumours available for follow-up progressed clinically, compared with 28 of 38 patients (74%) with p53 negative tumours. The median time to progression was 12 months in p53 positive tumours and 24 months in p53 negative tumours. Median survival in p53 positive tumours was 40 months, compared with 76 months in p53 negative tumours. This study demonstrates that overexpression of p53 in a small population of prostate cancers is associated with a poor prognosis in terms of progression and survival.
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PMID:p53 expression and clinical outcome in prostate cancer. 828 12


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