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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diagnostic and prognostic markers for prostatic cancer (PCa) include conventional protein markers (e.g., PAP, PSA, PSMA, PIP, OA-519, Ki-67, PCNA, TF, collagenase, and TIMP 1), angiogenesis indicator (e.g., factor VIII), neuroendocrine differentiation status, adhesion molecules (E-cadherin, integrin), bone matrix degrading products (e.g., ICPT), as well as molecular markers (e.g., PSA, PSMA, p53, 12-LOX, and MSI). Currently, only PSA is used clinically for early diagnosis and monitoring of PCa. The histological differential diagnosis of prostatic adenocarcinoma includes normal tissues such as Cowper's gland, paraganglion tissue and seminal vesicle or ejaculatory duct as well as pathological conditions such as atypical adenomatous hyperplasia, atrophy, basal cell hyperplasia and sclerosing adenosis. A common PCa is characterized by a remarkable heterogeneity in terms of its differentiation, microscopic growth patterns and biological aggressiveness. Most PCa are multifocal with signi ficant variations in tumor grade between anatomically separated tumor foci. The Gleason grading system which recognizes five major grades defined by patterns of neoplastic growth has gained almost uniform acceptance. In predicting the biologic behavior of PCa clinical and pathological stages are used as the major prognostic indicators. Among the cell proliferation and death regulators androgens are critical survival factors for normal prostate epithelial cells as well as for the androgen-dependent human prostatic cancer cells. The androgen ablation has been shown to increase the apoptotic index in prostatic cancer patients and castration also promotes apoptotic death of human prostate carcinoma grown in mice. The progression of PCa, similarly to other malignancies, is a multistep process, accompanied by genetic and epigenetic changes, involving phenomenons as adhesion, invasion and angiogenesis (without prostate specific features).
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PMID:Prostate Cancer - Old Problems and New Approaches. (Part II. Diagnostic and Prognostic Markers, Pathology and Biological Aspects). 1117 6

Functional overexpression of Bcl-2 has been reported to confer an anti-apoptotic potential in a variety of cell types. The role of Bcl-2 in epithelial cell-cycle control and in interactions with other cell-cycle regulators is not clearly understood. Its expression has been correlated with the hormono- and chemo-resistant phenotype in advanced prostate cancer. The aim of this study was to investigate the mechanisms through which Bcl-2 mediates increased cytotoxic chemoresistance by assessing alterations in the expression of cell death regulatory molecules. The DU145 human prostatic adenocarcinoma cell line was stably transfected with a Bcl-2 encoding expression plasmid. Two Bcl-2 transfectants, DKC9 and DKC11, were expanded for further study. The effects of Bcl-2 expression on cellular proliferation, cell death (+/- adriamycin or thapsigargin), and expression of cell-cycle/death regulators (p53, PCNA, Bax, Bak, Bcl-X(L)) were evaluated. Compared with controls, Bcl-2 transfectants showed no difference in the rate of proliferation, a decrease in p53 (approximately two-fold), an increase in Bax (approximately two-fold) and PCNA (approximately three-fold), and no change in the levels of Bcl-X(L) and Bak proteins. DKC9 and DKC11 also exhibited a significantly increased chemoresistance to adriamycin (0.0025-5 microM) and thapsigargin (0.0025-5 microM) compared with controls. In the presence of thapsigargin or adriamycin, levels of Bcl-2 and its heterodimeric partner Bax were elevated approximately two-fold with no change in Bak in Bcl-2 transfectants in contrast to controls, where Bak was increased (two-fold). This is the first study to demonstrate that Bcl-2 transfection modulates the expression of mutant p53, Bax, and PCNA in prostate cancer cells. Moreover, Bcl-2 overexpression conferred a significant cytotoxic chemoresistance and altered the balance of expression of death promoters (from Bak, a dominant death promoter in controls, to Bax) in response to thapsigargin and adriamycin.
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PMID:Differential expression of cell death regulators in response to thapsigargin and adriamycin in Bcl-2 transfected DU145 prostatic cancer cells. 1127 13

Diagnostically reliable identification of prostatic basal cells has depended on staining for high molecular weight cytokeratin. The diagnosis of malignancy is often based on the absence of basal cells. False-negative staining is occasionally observed. Thus, a second method of identifying basal cells might prove useful. Selective expression of p63, a homologue of p53, has been demonstrated in prostatic basal cells. We investigated the diagnostic utility of p63 staining in 70 consecutive specimens for which the differential diagnosis included prostatic adenocarcinoma: 68 needle biopsies and 2 transurethral resection blocks. High molecular weight cytokeratin staining was the gold standard when material was available. A total of 61 specimens were diagnosed as carcinoma, 4 as atrophy, 2 as high-grade prostatic intraepithelial neoplasia, 2 as unclassified collections of benign glands, and 1 as carcinoma versus high-grade prostatic intraepithelial neoplasia. Sections mounted on charged slides were used for p63 staining for 14 specimens. Sections previously hematoxylin and eosin stained on uncharged slides were used for 56 specimens. In every case in which there was successful p63 staining (55 specimens), basal cells in benign lesions were properly marked and other cell types were not stained. Uninformative staining in the remaining 15 specimens was due to failure of tissue adherence in 14 specimens in which sections were on uncharged slides and, in 1 specimen, to poor positive internal control staining of benign glands. Thus, p63 staining was informative in 55 of 56 specimens (98%) for which there was material for examination. No case with satisfactory p63 and high molecular weight staining showed disagreement between the two stains. An additional group of 21 transurethral resection specimens was stained (p63 and high molecular weight cytokeratin). There was less false-negative staining for p63 compared with the case of high molecular weight cytokeratin. No false-positive staining was seen. We conclude that p63 staining is at least as sensitive and specific for the identification of basal cells in diagnostic prostate specimens as is high molecular weight cytokeratin staining.
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PMID:Diagnostic utility of immunohistochemical staining for p63, a sensitive marker of prostatic basal cells. 1248 Oct 11

Pathologic characteristics of the prostatic adenocarcinoma in Koreans are not clear. We studied 132 cases of prostatectomy specimens using mapping analysis to discover the pathologic characteristics of the Korean prostatic adenocarcinoma. Mean values were as follows: serum prostate-specific antigen level (sPSA), 16.4 ng/ml; tumor volume, 27.5%; size, 2.4 cm; Gleason score, 7.7; and p53 expression, 9.8%. Rates of multifocal tumors and high-grade prostatic intraepithelial neoplasm (HPIN) were 33.3 and 65.2%. The Gleason score, tumor volume%, tumor size and sPSA were correlated with each other. Korean prostatic adenocarcinomas showed higher Gleason scores, lower rates of HPIN and multifocality, and lower p53 expression in comparison to Western prostatic adenocarcinomas. These data may be a basis for pathologic characteristics of Korean prostatic adenocarcinoma that has now been increasing.
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PMID:Pathologic characteristics of prostatic adenocarcinomas: a mapping analysis of Korean patients. 1280 73

We report the case of a 59-year-old man with a metachronous development of phyllodes tumor and adenocarcinoma of the prostate. He complained of urinary obstruction and transurethral resections of the prostate (TUR-P) had been performed six times in 10 years. Microscopic examination showed cystically dilated glands consisting of bizarre cells with pleomorphic, hyperchromatic nuclei in the stroma at the sixth TUR-P. Radical prostatectomy was performed against recurrences and adenocarcinoma was incidentally detected. Apparent up-regulation of proliferative nuclear antigens (PCNA), but not p53, was observed in the prostatectomy specimen by Western blotting. Active proliferation of stromal cells is considered to have caused the recurrent obstructive symptom.
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PMID:Phyllodes tumor of the prostate: recurrent obstructive symptom and stromal proliferative activity. 1537 51

Neuroendocrine (NE) differentiation in prostate cancer is typically detected by immunohistochemistry as single cells in conventional adenocarcinoma. Prostatic NE tumors, such as carcinoid or small cell carcinoma, are rare and large cell NE carcinoma (LCNEC) is described only in case reports. We identified 7 cases of LCNEC and compiled their clinicopathologic characteristics. In 6 cases, there was a history of adenocarcinoma treated with hormone therapy for a mean of 2.4 years (range: 2 to 3 y). The remaining case was de novo LCNEC. LCNEC was incidentally diagnosed in palliative transurethral resection specimens in 5 cases. The mean patient age at diagnosis with LCNEC was 67 years (range: 43 to 81 y). LCNEC comprised solid sheets and ribbons of cells with abundant pale to amphophilic cytoplasm, large nuclei with coarse chromatin and prominent nucleoli along with brisk mitotic activity and foci of necrosis. In 6 cases, there were foci of admixed adenocarcinoma, 4 of which showed hormone therapy effects. LCNEC was strongly positive for CD56, CD57, chromogranin A, synaptophysin, and P504S/alpha methylacyl CoA racemase. There was strong bcl-2 overexpression, expression of MIB1, and p53 in >50% of nuclei, focally positive staining for prostate specific antigen and prostatic acid phosphatase and negative androgen receptor staining. Follow-up was available for 6 patients, all of who died with metastatic disease at mean of 7 months (range: 3 to 12 mo) after platinum-based chemotherapy. LCNEC of prostate is a distinct clinicopathologic entity that typically manifests after long-term hormonal therapy for prostatic adenocarcinoma and likely arises through clonal progression under the selection pressure of therapy.
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PMID:Large cell neuroendocrine carcinoma of prostate: a clinicopathologic summary of 7 cases of a rare manifestation of advanced prostate cancer. 1672 45

Lipofuscin, known as the "wear and tear" pigment, is seen in cells undergoing regressive changes, the seminal vesicles and the ejaculatory ducts. It is also present in prostatic adenocarcinoma. The purpose of this study is to evaluate the prognostic significance of lipofuscin in prostatic adenocarcinoma. Lipofuscin was evaluated in 736 hematoxylin-eosin-stained slides from 60 conventional and whole-mounted consecutive radical prostatectomies from December 1996 to February 2002. The adenocarcinoma cases were divided into lipofuscin-positive group and lipofuscin-negative group. The Gleason score and pathologic stage were compared between the 2 groups. Percentage of cells positive for p53 and MIB-1 was also compared. Lipofuscin pigment was found in 17 (31%) of 60 prostatic adenocarcinomas as random, sparse, fine, yellow-brown intracytoplasmic granules staining positive for cathepsin D and negative for S-100 protein. Using logistic regression to exclude age as a confounding factor, lower Gleason scores and pathologic stages were demonstrated in the lipofuscin-positive group. There was also a significant difference between the 2 groups in tumor volume, degree of capsular invasion, and positive margins. The difference in seminal vesicle invasion and vascular invasion between the 2 groups was not statistically significant. Lipofuscin in prostatic adenocarcinoma correlates with both lower Gleason score and pathologic stage. Lipofuscin probably indicates slow cellular turnover as suggested by the low proliferation rate and p53 expression. The value of lipofuscin in biopsy as a predictor separating aggressive from indolent disease needs further investigation.
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PMID:Lipofuscin pigment can be used as a prognostic marker in prostatic adenocarcinoma. 1697 16

The differential diagnosis between carcinoma of the urinary bladder and adenocarcinoma of the prostate can be difficult, especially in the poorly differentiated forms infiltrating the neighboring organs. In this article, the authors report 2 cases that pose a diagnostic dilemma to the pathologist. The first is an infiltration of the bladder by a poorly differentiated adenocarcinoma of the prostate, which was clinically suspected as a papillary urothelial neoplasm. The second is a collision tumor composed of prostatic adenocarcinoma and urothelial carcinoma observed on a core needle biopsy of the prostate. In both cases, a large panel of immunohistochemical markers were used and demonstrated positivity for prostate-specific antigen and alpha methyl racemase in the prostatic carcinomas and immunoreactivity for CK7, CK20, Ag 34betaE12, and p53 in the urothelial carcinoma. The differentiating histological and immunohistochemical findings are discussed.
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PMID:Poorly differentiated adenocarcinomas of prostate versus high-grade urothelial carcinoma of the bladder: a diagnostic dilemma with immunohistochemical evaluation of 2 cases. 1747 86

We report 2 patients with conventional prostatic adenocarcinoma who developed sarcomatoid carcinoma of probable prostatic origin 6 and 2.5 years after radiation treatment (seed implantation and external beam). Our cases had histologic features consistent with those cases previously reported in the literature. The tumors consisted of spindle cells with large hyperchromatic nuclei and a pattern mimicking a sarcoma. Immunohistochemical studies showed the tumors to be weakly positive for EMA, CK7, and vimentin. Ki67 staining showed positivity in more than 50% of tumor cells. The tumors also stained diffusely positive for p53 and p63. PSA and PAP were negative. Clinically, the sarcomatoid carcinomas appeared to be of prostatic origin. The pathogenesis of the tumors is still uncertain but most likely represent a radiation-induced dedifferentiation of prostatic adenocarcinoma.
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PMID:Sarcomatoid carcinoma after radiation treatment of prostatic adenocarcinoma. 1832 77

Numerous studies have demonstrated the apoptotic index to be significantly higher in benign prostatic lesions than in PIN and adenocarcinoma. Furthermore, a lower apoptotic index in epithelial cell populations has been shown to correlate with decreased immunoreactivity for prostate specific antigen that may be seen in higher Gleason grade tumors. It is suggested that the loss of function of some apoptotic regulators contributes to the development of PIN and prostatic adenocarcinoma. Of these, three signaling molecules involved in apoptotic functions ofTGF-beta have now been intensively investigated, including transmembrane receptor II (T betaRII), cell cycle inhibitor p27(Kp1) and Smad4, effectors of TGF-beta signaling pathway. Increased expression of p53 and decreased expression of maspin, a serine protease inhibitor, also play a major role in the apoptotic process. Changes in the expression of these markers may serve as a reliable criterion on making the diagnosis in biopsy material and may help choose an appropriate therapeutic approach.
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PMID:[Apoptosis in pathologic prostatic processes]. 1999 47


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