Quantitative multi-gene expression profiling of primary prostate cancer

Schmidt, Frank; Fuessel, Susanne; Koch, Rainer; Baretton, Gustavo; Lohse, Andrea; Tomasetti, S.; Unversucht, S.; Froehner, Michael; Wirth, Manfred P.; Meye, Axel

doi:10.1002/pros.20490

Cited by 114 publications

(94 citation statements)

References 51 publications

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“…There is a general consensus that EZH2 overexpression aggravates during prostate cancer progression. In metastases, even gene amplification is found and associated with strong overexpression, 42 whereas the increases in primary cases are usually moderate, 24,40,44 as in the present study, or are even undetectable. 25 However, the moderate increases in nonmetastatic cancers might be difficult to detect by the RNA-in-situ-hybridization technique used in ref.…”

Section: © 2 0 0 8 L a N D E S B I O S C I E N C E D O N O T D I S supporting

confidence: 70%

“…Turning-point values for the specific genes were related to those for TBP, the most stable housekeeping gene in prostate cancer. 44 Immunohistochemistry. For EZH2, DNMT1 and DNMT3B stainings paraffin sections were treated with xylene and ethanol.…”

Section: Patients Materials and Methodsmentioning

confidence: 99%

“…Its expression increases gradually during prostate cancer progression and is maximal in metastatic cases. 24,[40][41][42][43][44] Despite numerous descriptive studies, the effects of EZH2 overexpression in prostate cancer are poorly understood. On BMI-1, only two, very recent studies 40,41 have been published and none on SIRT1 in human cancers.…”

Section: Introductionmentioning

confidence: 99%

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Expression changes in EZH2, but not in BMI-1, SIRT1, DNMT1 or DNMT3B are associated with DNA methylation changes in prostate cancer

Hoffmann

Engers

Florl³

et al. 2007

Cancer Biology & Therapy

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The polycomb proteins BMI-1, EZH2 and SIRT1 are characteristic components of the PRC1, PRC2 and PRC4 repressor complexes, respectively, that modify chromatin. Moreover, EZH2 may influence DNA methylation by direct interaction with DNA methyltransferases. EZH2 expression increases during prostate cancer progression, whereas BMI-1 and SIRT1 are not well investigated. Like EZH2 expression, DNA methylation alterations escalate in higher stage prostate cancers, raising the question whether these epigenetic changes are related. Expression of EZH2, BMI-1, SIRT1 and the DNA methyltransferases DNMT1 and DNMT3B measured by qRT-PCR in 47 primary prostate cancers was compared to APC, ASC, GSTP1, RARB2 and RASSF1A hypermethylation and LINE-1 hypomethylation. SIRT1 and DNMT3B were overexpressed in cancerous over benign tissues, whereas BMI-1 was rather downregulated and DNMT1 significantly diminished. Nevertheless, cancers with higher DNMT1 and BMI-1 expression had worse clinical characteristics, as did those with elevated EZH2. In particular, above median DNMT1 expression predicted a worse prognosis. EZH2 and SIRT1 overexpression were well correlated with increased MKI67. Immunohistochemistry confirmed limited EZH2 and heterogeneous DNMT3B overexpression and explained the decrease in BMI-1 by pronounced heterogeneity among tumor cells. EZH2 overexpression, specifically among all factors investigated, was associated with more frequent hypermethylation, in particular of GSTP1 and RARB2 and also with LINE-1 hypomethylation. Our data reveal complex changes in the composition of polycomb repressor complexes in prostate cancer. Heterogeneously expressed BMI-1 and slightly increased EZH2 may characterize less malignant cancers, whereas more aggressive cases express both at higher levels. SIRT1 appears to be generally increased in prostate cancers. Intriguingly, our data suggest a direct influence of increased EZH2 on altered DNA methylation patterns in prostate cancer.

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Section: © 2 0 0 8 L a N D E S B I O S C I E N C E D O N O T D I S supporting

confidence: 70%

Section: Patients Materials and Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Expression changes in EZH2, but not in BMI-1, SIRT1, DNMT1 or DNMT3B are associated with DNA methylation changes in prostate cancer

Hoffmann

Engers

Florl³

et al. 2007

Cancer Biology & Therapy

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“…In a study on nine prostate-related transcripts, PCA3 was found as the best single marker for the detection of prostate carcinoma. 17 Using laser microdissection, Thelen et al 18 detected PCA3 RNA by RT-PCR in all analyzed On a large cohort of 517 patients, Fradet et al 23 demonstrated that uPM3, a test detecting PCA3 and PSA mRNA in urine samples, can be a useful adjunct to current methods for the detection of early prostate cancer. The overall sensitivity and specificity were 66 and 89%, respectively; the positive predictive value was 75% and the negative predictive value was 84%.…”

Section: Discussionmentioning

confidence: 99%

Identification of PCA3 (DD3) in prostatic carcinoma by in situ hybridization

et al. 2007

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PCA3 is a specific marker of prostatic carcinoma. However, PCA3 has been detected only at RNA level and a corresponding PCA3 protein has never been identified. The aim of this study was to develop a technique capable of detecting PCA3 RNA on histology sections and to assess the cellular location of the molecule. Fortyeight formalin-fixed paraffin-embedded blocks of prostatectomy specimens were selected for PCA3 detection by in situ hybridization by both radioactive and chromogenic methods. Of the 48 sections, 28 contained prostatic adenocarcinoma and 20 had benign tissue located distant from the tumor. Using the radioactive detection method, 26 of 28 available cases (93%) of cancers presented at least focal cytoplasmic PCA3 expression. The benign glands located in proximity of the cancer presented PCA3 expression in eight (29%) cases, whereas those situated distant to the tumor showed focal expression in 2 of 20 (10%) cases only. Highgrade prostatic intraepithelial neoplasia (HGPIN) expressed PCA3 in 25 of 26 (96%) cases. With the chromogenic detection method, 22 of the 24 interpretable cases (92%) of cancers had at least focal cytoplasmic staining. Benign glands located close to neoplastic glands expressed PCA3 in 8 (33%) cases, but none of those distant to the tumor expressed the marker. HGPIN was positive in 17 of 24 (71%) cases. The sensitivity, specificity, positive predictive value and negative predictive value for the detection of cancer were 93, 79, 71 and 95% for the radioactive detective method and 92, 80, 71 and 95% for the chromogenic detection method, respectively. Our study shows that PCA3 RNA is expressed by most prostate cancers and HGPIN. Normal glands rarely express the marker, except those located in immediate proximity of neoplastic glands, suggesting the presence of precursor molecular changes.

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“…Most importantly, it does not ignore the heterogeneity of CaP and can detect prostate cancer more accurately than single marker tests. 70,71 Recent studies have characterized the clonality and heterogeneity of TMPRSS2/ERG fusion in multifocal CaP. 57,72 Both interfocal heterogeneity and intrafocal homogeneity for TMPRSS2/ERG fusion have been found in multifocal CaP in the radical prostatectomy specimens.…”

Section: Multiplex Analysis Of Urine Markers and Future Directionsmentioning

confidence: 99%

Urine markers in monitoring for prostate cancer

Jamaspishvili

Král

Khomeriki

et al. 2009

Prostate Cancer Prostatic Dis

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The major advantages of urine-based assays are their noninvasive character and ability to monitor prostate cancer with heterogeneous foci. Almost all urine-detectable prostate-specific markers have been recently reviewed. For this reason, we focus here on only a few promising markers which have been independently evaluated (in particular PCA3, fusion genes, TERT, AMACR, GSTP1, MMP9 and VEGF) and very recent ones (ANXA3 and sarcosine). The emphasis is also on multiplex biomarker analysis and on microarray-based analysis of fusion genes. A combination of multiple urine biomarkers may be valuable in the case of men with persistently elevated serum prostatespecific antigen and a history of negative biopsies. The emerging urine tests should help in both early diagnosis of prostate cancer and identifying aggressive tumors for radical treatment.

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Quantitative multi-gene expression profiling of primary prostate cancer

Cited by 114 publications

References 51 publications

Expression changes in EZH2, but not in BMI-1, SIRT1, DNMT1 or DNMT3B are associated with DNA methylation changes in prostate cancer

Expression changes in EZH2, but not in BMI-1, SIRT1, DNMT1 or DNMT3B are associated with DNA methylation changes in prostate cancer

Identification of PCA3 (DD3) in prostatic carcinoma by in situ hybridization

Urine markers in monitoring for prostate cancer

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