Specific detection of prostate cancer cells in urine by multiplex immunofluorescence cytology

Fujita, Kazutoshi; Pavlovich, Christian P.; Netto, George J.; Konishi, Yuko; Isaacs, William B.; Ali, Syed Abbas; Marzo, Angelo De; Meeker, Alan K.

doi:10.1016/j.humpath.2009.01.004

Cited by 43 publications

(41 citation statements)

References 30 publications

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“…Urine cytological examination can diagnose the cells as malignant, but it is difficult to determine their origin; that is, whether the malignant cells originate from urothelial carcinoma or prostate cancer. Multiple staining of the precipitates of urine after prostate massage for AMACR, Nkx3.1, nucleolin and 4′‐6‐diamidino‐2‐phenylindole to detect prostate cancer cells in urine was also carried out . Upregulation of AMACR and downregulation of Nkx3.1 were specific for prostate cancer, and the upregulation of nucleolin was a characteristic of the malignant cells.…”

Section: Prostate Cancer Cells In Urinementioning

confidence: 97%

Urinary biomarkers of prostate cancer

2018

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The development of more specific biomarkers for prostate cancer and/or high-risk prostate cancer is necessary, because the prostate-specific antigen test lacks specificity for the detection of prostate cancer and can lead to unnecessary prostate biopsies. Urine is a promising source for the development of new biomarkers of prostate cancer. Biomarkers derived from prostate cancer cells are released into prostatic fluids and then into urine. Urine after manipulation of the prostate is enriched with prostate cancer biomarkers, which include prostate cancer cells, DNAs, RNAs, proteins and other small molecules. The urinary prostate cancer antigen 3 test is the first Food and Drug Administration-approved RNA-based urinary marker, and it helps in the detection of prostate cancer on repeat biopsy. The SelectMDx test is based on messenger RNA detection of DLX1 and HOXC6 in urine after prostate massage, and helps in the detection of high-risk prostate cancer on prostate biopsy. Exosomes are extracellular vesicles with a diameter of 30-200 nm that are secreted from various types of cells. Urinary prostate cancer-derived exosomes also contain RNAs and proteins specific for prostate cancer (e.g. PCA3 and TMPRSS2-ERG), and could be promising sources of novel biomarker discovery. The ExoDx Prostate test is a commercially available test based on the detection of three genes (PCA3, ERG and SPDEF) in urinary exosomes. Advancement of comprehensive analysis (microarray, mass spectrometry and next-generation sequencing) has resulted in the discovery of several urinary biomarkers. Non-invasive urinary markers can help in the decision to carry out prostate biopsy or in the design of a therapeutic strategy.

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Section: Prostate Cancer Cells In Urinementioning

confidence: 97%

Urinary biomarkers of prostate cancer

2018

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“…Attempts at detecting individual PCa cells in urine by using cytology are thwarted by unacceptably low sensitivities, although specificities are high. 11 Studies have estimated that only 10% of cells in the urine are of prostate origin and previous attempts at using a multiplex panel of markers in combination with cytology only reached a sensitivity of 15% for PCa detection. 11 Furthermore, when found cytologically, PCa cells in the urine occur almost exclusively in patients with high grade or advanced cancers.…”

Section: Resultsmentioning

confidence: 99%

“…11 Studies have estimated that only 10% of cells in the urine are of prostate origin and previous attempts at using a multiplex panel of markers in combination with cytology only reached a sensitivity of 15% for PCa detection. 11 Furthermore, when found cytologically, PCa cells in the urine occur almost exclusively in patients with high grade or advanced cancers. 12 Of interest, the presence of PCa cells may not be required for all urine-based assays, since DNA can also pass into urine via phagocytosis (i.e.…”

Section: Resultsmentioning

confidence: 99%

Toward the Detection of Prostate Cancer in Urine: A Critical Analysis

2013

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Introduction Prostate specific antigen (PSA) and digital rectal exam (DRE) have low specificity for the detection of prostate cancer (PCa) and poorly predict the presence of aggressive disease. Urine is readily available, non-invasive, and represents a promising source of biomarkers for early detection and prediction of PCa prognosis. The goal of this review is to identify promising biomarkers for urine-based PCa, examine trends, and outline potential pitfalls. Methods Pubmed® and Web of Science® database searches of peer-reviewed literature on urine-based testing in PCa were performed. Original studies on this subject, as well as a small number of reviews, were analyzed including the strengths and weaknesses. We provide a comprehensive review of urine-based testing for PCa that covers the technical aspects including the methodology of urine collection, as well as recent developments in biomarkers spanning the fields of genomics, epigenetics, transcriptomics, proteomics, and metabolomics. Results The process of urine collection is subject to variability, which may result in conflicting clinical results. Detecting PCa in urine is technically feasible as demonstrated by numerous “proof-of principle” studies, but few markers have been validated in multiple large sample sets. Biomarker development using urine has been accelerating in recent years, with numerous studies identifying DNA, RNA, protein, and metabolite-based biomarkers in the urine. Advanced clinical studies have identified PCA3 and TMPRSS2:ERG fusion transcripts as promising RNA markers for cancer detection and possibly prognosis. DNA methylation analysis of multiple genes improves specificity, and represents a promising platform for the development of clinical-grade assays. Conclusions Urine-based testing is non-invasive and represents a rich source of novel biomarkers for PCa. Although urine demonstrates promise in detecting cancer, the ability to identify aggressive subsets of PCa needs further development.

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“…Urine is likely to become an increasingly powerful source of prostate-specific biomarkers [9][10][11][12]. Urine after DRE contains various markers originating from the prostate, including cytokines10, RNAs [13], DNAs [14], and prostate cells [11].…”

Section: Discussionmentioning

confidence: 99%

“…Urine after DRE contains various markers originating from the prostate, including cytokines10, RNAs [13], DNAs [14], and prostate cells [11]. MCP-1 was assayed in the urine after DRE in order to sample the prostatic microenvironment most directly.…”

Section: Discussionmentioning

confidence: 99%

Prostatic Monocyte Chemotactic Protein-1 (MCP-1): A Novel Potential Biomarker for Symptomatic Benign Prostatic Hyperplasia

Fujita¹,

Kellogg²,

Charles³

et al. 2017

MCMR

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Abstract. Monocyte chemotactic protein-1 (MCP-1) is differentially expressed in benign prostatic hyperplasia (BPH) and is a potential clinical biomarker for BPH. We collected urine post-digital rectal examination (DRE) from 48 men who did not have a diagnosis of prostate cancer. We measured MCP-1 levels by enzyme-linked immunosorbent assay (ELISA) and compared them with prostate weight and lower urinary tract symptoms (LUTS) as measured by the International Prostate Symptom Score (I-PSS) utilizing correlation and regression analyses. In post-DRE urine, higher MCP-1 levels were associated with increased I-PSS but not with prostate volume. MCP-1 levels in men with prostate enlargement were significantly higher than those in men without enlargement. In multivariable regression adjusting for age, prostate volume, and PSA,higher urinary MCP-1 was associated with significantly higher I-PSS. Since MCP-1 is preferentially expressed in BPH tissue, these data suggest that MCP-1 may be a novel biomarker for clinically significant BPH.Keywords: MCP-1, LUTS, urine marker, benign prostatic hyperplasia IntroductionBenign prostate hyperplasia (BPH) is a common disease affecting older men caused by unregulated prostatic stromal and epithelial growth resulting in prostate enlargement, bladder outlet obstruction, and lower urinary tract symptoms (LUTS) [1]. Despite intensive researches over the last several decades, the molecular mechanisms underlying prostatic enlargement and symptomatic bladder outlet obstruction remain obscure, and specific clinical markers for symptomatic BPH have yet to be developed. We previously used a human cytokine array to search for cytokines in expressed prostatic secretions (EPS) from radical prostatectomy specimens that may be associated with prostate enlargement, and found that monocyte/macrophage chemoattractant protein-1 (MCP-1, CCL2) in EPS was associated with prostate size [2]. MCP-1 is a member of the CC chemokine superfamily and plays a critical role in the recruitment and activation of monocytes during inflammation [3]. MCP-1 is secreted from prostatic stromal cells and stimulates the proliferation of prostatic epithelial cells in vitro. Immunohistochemical studies indicated that MCP-1 was upregulated in benign prostatic hyperplasia (BPH) lesions, and MCP-1 levels in EPS correlated with mRNA levels of the macrophage marker CD68 [4]. Based on these data, we hypothesize that MCP-1 levels in urine after DRE, which is enriched in prostatic contents, could serve as a specific clinical marker for symptomatic BPH. Therefore, we evaluated associations of MCP-1 levels in urine collected after DRE with prostate volume and LUTS by enzyme-linked immunosorbent assay (ELISA).

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Specific detection of prostate cancer cells in urine by multiplex immunofluorescence cytology

Cited by 43 publications

References 30 publications

Urinary biomarkers of prostate cancer

Urinary biomarkers of prostate cancer

Toward the Detection of Prostate Cancer in Urine: A Critical Analysis

Prostatic Monocyte Chemotactic Protein-1 (MCP-1): A Novel Potential Biomarker for Symptomatic Benign Prostatic Hyperplasia

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