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)

The development of prostate cancer is believed to be a multistep process, progressing sequentially from normal epithelium, to prostatic intraepithelial neoplasia (PIN) and, finally, to invasive neoplasia. Malignant stem cells within the basal cell layer of the prostatic epithelium are believed to play an important role in the failure of androgen-ablation therapy that occurs in the most advanced form of prostate cancer. The aim of the present study was to immunohistochemically characterize the lesions of canine PIN. Prostatic tissue from five dogs with PIN was compared with normal prostate tissue from nine further dogs. There was an increase in the number of basal epithelial cells in lesions consistent with PIN as defined by expression of the nuclear protein p63. These lesions had elevated expression of proliferating cell nuclear antigen (PCNA) and heterogeneous labelling for the nuclear androgen receptor (AR). These findings suggest that the basal cells present in PIN may play a role in canine prostate carcinogenesis and that the proliferation of these cells occurs despite the heterogeneous expression of the AR.
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PMID:Immunohistochemical characterization of canine prostatic intraepithelial neoplasia. 1964 31

Nephrogenic adenoma (NA) is a rare benign lesion of the urinary tract. Although its histogenesis is still debated, several reports suggest that the lesion has a renal tubular cell origin or differentiation. As NA can be difficult to distinguish from malignant conditions such as prostate cancer, there is a need for reliable markers. Unfortunately, it has been reported that NA cells also stained positive for the prostate cancer marker alpha-methylacyl-coenzyme A racemase (AMACR). Because all the previous studies have used an avidin-biotin (AB) detection procedure, and because cells with tubular renal differentiation are likely to contain a high level of endogenous biotin, we investigated in NA the expression of several markers including AMACR, using both AB and biotin-free detection systems. We assessed the expression of p63, cytokeratins 7 and 20, CD10 (proximal tubule marker), MUC1 (distal tubule marker), PAX2, and AMACR on 14 NAs (from 6 patients) grouped on a tissue microarray. The tissue microarray also included renal, urothelial, and prostate tissues. Staining was detected using both AB and biotin-free Envision systems. Detection with the AB procedure leads to nonspecific staining in kidney samples and NA. More specific expression was obtained by using the Envision kit, and only CK7, PAX2, and MUC1 remained positive in NA, without any AMACR staining. These findings provide supporting evidence that NA has the differentiation of distal renal tubules, and strongly suggest that AMACR, when detected with a biotin-free procedure, can be used as a reliable marker for distinguishing NA from prostate cancer.
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PMID:Revisiting the immunophenotype of nephrogenic adenoma. 1973 Mar 62

Immunohistochemistry has become an indispensible tool in biopsy diagnostics of prostate tissues. In particular the use of basal cell markers can be useful to differentiate benign and malignant lesions as a lack of basal cells is considered a hallmark of malignancy. Basal cell cytokeratins and p63 have therefore a long standing place in the diagnostic portfolio of most genito-urinary pathologists. However, to complement the use of these negative markers by additional positive immunohistochemistry markers of malignancy would be desirable to further increase diagnostic accuracy. The most widely used positive marker is alpha-methylacyl-CoA racemase (AMACR), which is strongly upregulated in prostate cancer and which can even be combined with p63 in a single immunostaining. This article briefly and critically reviews current diagnostic prostate cancer biomarkers and also suggests golgi phosphoprotein 2 (GOLPH2) and fatty acid synthase (FASN) as additional diagnostic markers.
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PMID:[Immunohistochemical algorithms in prostate diagnostics: what's new?]. 1979 24

We have shown previously that Pten deletion leads to the expansion of subset of prostate cancer cells positive for CK5 and p63. Although this subpopulation may be involved in tumor initiation or progression, studies to date have not functionally validated this hypothesis. Using in vitro sphere-forming assay and in vivo prostate reconstitution assay, we show here the presence of a tumor-initiating subpopulation in the Pten prostate cancer mouse model. Specifically, we show that the Lin(-)Sca-1(+)CD49f(high) (LSC) subpopulation overlaps with CK5(+);p63(+) cells and is significantly increased during prostate cancer initiation and progression and after castration. Mutant spheres mimic the structural organization of the epithelial compartment in the Pten-null primary tumor. Sorted LSC cells from either Pten-null spheres or primary tumors are able to regenerate prostate epithelial structure with cancerous morphology, closely mimicking that of primary cancers. Therefore, the LSC subpopulation is capable of initiating a cancerous phenotype that recapitulates the pathology seen in the primary lesions of the Pten mutant prostate model.
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PMID:Lin-Sca-1+CD49fhigh stem/progenitors are tumor-initiating cells in the Pten-null prostate cancer model. 1988 4

Early diagnosis of prostate cancer is one of the most important problems of modern oncology. Trepan biopsy and further histological investigation are the standards for examination of patients with prostate neoplasms. Our investigations of 56 cases have indicated that in 27% of the cases, histological investigation is insufficient to make a valid diagnosis. In such cases, immunohistochemical evaluation of the expression of high-molecular-weight cytokeratins and p63 allows differentiation of carcinoma from benign masses of the prostate, which may be used to enhance the efficiency of early diagnosis of prostate cancer.
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PMID:[Efficiency of immunohistochemical study of high-molecular-weight cytokeratins (CKR-HMW) and p63 in prostate trepan biopsy specimens for establishing the diagnosis of adenocarcinoma]. 2013 10

Previous studies indicated that EAF (ELL-associated factor) family members, EAF1 and EAF2/U19, play a role in cancer and embryogenesis. For example, EAF2/U19 may serve as a tumor suppressor in prostate cancer. At the same time, EAF2/U19 is a downstream factor in the non-canonical Wnt 4 signaling pathway required for eye development in Xenopus laevis, and along with EAF1, contributes to convergence and extension movements in zebrafish embryos through Wnt maintenance. Here, we used zebrafish embryos and mammalian cells to show that both EAF1 and EAF2/U19 were up-regulated by Wnt4 (Wnt4a). Furthermore, we found that EAF1 and EAF2/U19 suppressed Wnt4 expression by directly binding to the Wnt4 promoter as seen in chromatin immunoprecipitation assays. These findings indicate that an auto-regulatory negative feedback loop occurs between Wnt4 and the EAF family, which is conserved between zebrafish and mammalian. The rescue experiments in zebrafish embryos showed that early embryonic development required the maintenance of the appropriate levels of Wnt4a through the feedback loop. Others have demonstrated that the tumor suppressors p63, p73 and WT1 positively regulate Wnt4 expression while p21 has the opposite effect, suggesting that maintenance of appropriate Wnt4 expression may also be critical for adult tissue homeostasis and prevention against tumor initiation. Thus, the auto-regulatory negative feedback loop that controls expression of Wnt4 and EAF proteins may play an important role in both embryonic development and tumor suppression. Our findings provide the first convincing line of evidence that EAF and Wnt4 form an auto-regulatory negative feedback loop in vivo.
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PMID:Negative feedback regulation of Wnt4 signaling by EAF1 and EAF2/U19. 2016 47

The development of biomarkers for prostate cancer screening, detection and prognosis has greatly decreased the mortality of this disease. Recently, some new views on such biomarkers as PSMA, CK34betaE12, p63, AMACR, Pca-24, hTERT, DD3, Annexin A3 and GSTP1 methylation in prostate cancer tissue have been re-identified and investigated. Future research should focus on the combined screening of multiple biomarkers and discovery of new ones, which may possibly improve the sensitivity, specificity and accuracy of the early detection of prostate cancer.
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PMID:[An update of biomarkers in prostate cancer tissue]. 2021 20

NKX3.1 is a homeodomain protein that functions as a dosage sensitive prostate-specific transcription factor. Diminished NKX3.1 expression is associated with prostate epithelial cell proliferation in vitro and with increasing Gleason grade in patient samples. Mouse Nkx3.1 also functions as a negative regulator of prostate cell growth in prostate cancer models. Identifying biological and environmental factors that modulate NKX3.1 accumulation is therefore central to efforts aimed at elucidating prostate growth control mechanisms. To determine the effect of inflammation on Nxk3.1 accumulation, bacterial prostatitis was induced by intraurethral inoculation of a uropathogenic E. coli strain in mice. Nkx3.1 expression was profoundly reduced in infected prostate lobes and correlated with increased expression of a proliferation marker. Androgen receptor levels were also reduced in concert with Nkx3.1, and a marked increase in the basal cell marker p63 was observed. Analyses of the inflammatory infiltrate revealed a classic acute inflammatory response that attained characteristics of a chronic state within fourteen days postinoculation. Comparison of the four prostate lobes revealed clear differences in the extent of inflammation. These data demonstrate that acute inflammation in response to a bacterial agent in the prostate is associated with a significant diminution in the level of a key regulator of prostate cell proliferation. These observations provide a plausible mechanism whereby prostate inflammation may establish a local environment conducive to epithelial cell growth.
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PMID:Loss of Nkx3.1 expression in bacterial prostatitis: a potential link between inflammation and neoplasia. 2036 13

T-cell receptor gamma chain alternative reading frame protein (TARP) has recently been proposed as being up-regulated in prostate cancer (PCA). Additionally, TARP has been proposed as a potential therapeutic target for cancer therapy. We analysed the protein expression of TARP in a large well characterised prostate cancer cohort to assess its diagnostic and prognostic value. Methodologically, we constructed a tissue microarray comprising more than 600 PCA cases including matching benign prostate tissue. TARP protein expression was carefully analysed and associated with clinico-pathological parameters, PSA-relapse free survival and expression data of established and proposed diagnostic markers (AMACR, p63, GOLPH2). Our results show that TARP is significantly over-expressed in the vast majority (approximately 85%) of PCA in comparison to non neoplastic prostate tissue. Its expression was associated with conventional markers of unfavourable and more aggressive tumour behaviour. However, a prognostic value of TARP could not be found. The diagnostic value of TARP is limited in comparison to AMACR, p63 or GOLPH2. Since TARP specific immunologic therapy regimen are currently being tested, the high frequency of TARP over-expression in PCA conveys a high potential for a predictive and potentially therapeutic use of this biomarker.
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PMID:Diagnostic and prognostic value of T-cell receptor gamma alternative reading frame protein (TARP) expression in prostate cancer. 2037 79

Tumor heterogeneity is one of the most important and challenging problems not only in studying the mechanisms of cancer development but also in developing therapeutics to eradicate cancer cells. Here we report the use of multiplexed quantum dots (QDs) and wavelength-resolved spectral imaging for molecular mapping of tumor heterogeneity on human prostate cancer tissue specimens. By using a panel of just four protein biomarkers (E-cadherin, high-molecular-weight cytokeratin, p63, and alpha-methylacyl CoA racemase), we show that structurally distinct prostate glands and single cancer cells can be detected and characterized within the complex microenvironments of radical prostatectomy and needle biopsy tissue specimens. The results reveal extensive tumor heterogeneity at the molecular, cellular, and architectural levels, allowing direct visualization of human prostate glands undergoing structural transitions from a double layer of basal and luminal cells to a single layer of malignant cells. For clinical diagnostic applications, multiplexed QD mapping provides correlated molecular and morphological information that is not available from traditional tissue staining and molecular profiling methods.
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PMID:Molecular mapping of tumor heterogeneity on clinical tissue specimens with multiplexed quantum dots. 2037 68


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