Current practice of Gleason grading of prostate carcinoma

López-Beltrán, Antonio; Mikuz, Gregor; Luque, Rafael J.; Mazzucchelli, Roberta; Montironi, Rodolfo

doi:10.1007/s00428-005-0102-4

Cited by 54 publications

(33 citation statements)

References 47 publications

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“…The Gleason score is expressed as the sum of the two most prominent Gleason patterns. A Gleason score >7 is correlated with a highly malignant tumor whereas a low Gleason score ≤7 is an indicator of less agressive disease (41,42). our study population included 3 patients with a Gleason score >7.…”

Section: Resultsmentioning

confidence: 99%

BRCA1, BRCA2, AR and IGF-I expression in prostate cancer: Correlation between RT-qPCR and immunohistochemical detection

Rabiau

Déchelotte²,

Adjakly³

et al. 2011

Oncol Rep

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Abstract. Identification and characterization of biomarkers in prostate cancer are important for improving the diagnosis. The aim of this study was to determine differences in the expression of 4 genes according to the stage of malignancy in prostate cancer. We analyzed BRCA1, BRCA2, androgen receptor (AR) and IGF-I gene expression in a cohort of 98 prostate biopsies. We used TaqMan RT-qPCR for mRNA detection, and correlation with proteins was performed using immunohistochemistry. Among the 98 studied prostate biopsies, high heterogeneity in the expression of the 4 genes was detected among the different histological types. However, down-regulation of BRCA1 and BRCA2 mRNA was detected, particularly in the normal tissues. The expression of AR was dependent on the stage of the tumor. The IGF-I gene was specifically expressed in the tumor tissues. Upon comparison between protein and mRNA expression for BRCA1, BRCA2 and AR, we obtained a trend; however, this did not achieve statistical significance. Regarding IGF-I, a correlation between mRNA expression and staining intensity of the protein was found to be significant (p<0.012). The AR biomarker was found to be slightly correlated with the prostate cancer diagnosis (p=0.013). AR was found to be decreased in the tumors with a 43% sensitivity and 90% specificity. The relative risk of 2.05 (1.13-3.69) indicated a 2-fold higher chance of cancer occurence when AR was ≤0.206.

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Section: Resultsmentioning

confidence: 99%

BRCA1, BRCA2, AR and IGF-I expression in prostate cancer: Correlation between RT-qPCR and immunohistochemical detection

Rabiau

Déchelotte²,

Adjakly³

et al. 2011

Oncol Rep

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“…To reflect the morphologic heterogeneity of a prostate cancer, the Gleason score (ranging from 2 to 10) is composed of the two most dominant architectural patterns, which are numbered 1 to 5. If only one pattern is present, this is doubled to give the Gleason score (5,6).…”

Section: Introductionmentioning

confidence: 99%

Altered DNA Methylation Landscapes of Polycomb-Repressed Loci Are Associated with Prostate Cancer Progression and ERG Oncogene Expression in Prostate Cancer

Kron

Trudel

Pethe

et al. 2013

Clinical Cancer Research

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Purpose: To assess differentially methylated "landscapes" according to prostate cancer Gleason score (GS) and ERG oncogene expression status, and to determine the extent of polycomb group (PcG) target gene involvement, we sought to assess the genome-wide DNA methylation profile of prostate cancer according to Gleason score and ERG expression.Experimental Design: Genomic DNA from 39 prostate cancer specimens was hybridized to CpG island microarrays through differential methylation hybridization. We compared methylation profiles between Gleason score and ERG expression status as well as Gleason score stratified by ERG expression status. In addition, we compared results from our dataset to publicly available datasets of histone modifications in benign prostate cells.Results: We discovered hundreds of distinct differentially methylated regions (DMR) associated with increasing Gleason score and ERG. Furthermore, the number of DMRs associated with Gleason score was greatly expanded by stratifying samples into ERG-positive versus ERG-negative, with ERG-positive/GSassociated DMRs being primarily hypermethylated as opposed to hypomethylated. Finally, we found that there was a significant overlap between either Gleason score-related or ERG-hypermethylated DMRs and distinct regions in benign epithelial cells that have PcG signatures (H3K27me3, SUZ12) and lack active gene expression signatures (H3K4me3, RNA pol II).Conclusions: This work defines methylation landscapes of prostate cancer according to Gleason score, and suggests that initiating genetic events may influence the prostate cancer epigenome, which is further perturbed as prostate cancer progresses. Moreover, CpG islands with silent chromatin signatures in benign cells are particularly susceptible to prostate cancer-related hypermethylation.

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“…Pure pattern 3 (GS 6) PCas are low grade, whereas pure pattern 4 (GS 8) cancers are high grade. 5 GS 7 cancers (composed of glandular patterns 3 and 4 in variable amounts) are considered intermediate grade. Pretreatment identification of GS 7 cancers (ie presence of Gleason pattern 4) is considered key to distinguish indolent or clinically insignificant PCa from those that require treatment.…”

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confidence: 99%

DNA methylation of HOXD3 as a marker of prostate cancer progression

Kron

Liu

Pethe

et al. 2010

Laboratory Investigation

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DNA methylation in gene promoters causes gene silencing and is a common event in cancer development and progression. The ability of aberrant methylation events to serve as diagnostic and prognostic markers is being appreciated for many cancers, including prostate cancer. Using quantitative MethyLight technology, we evaluated the relationship between HOXD3 methylation and clinicopathological parameters including biochemical recurrence, pathological stage, Gleason score (GS), and Gleason pattern in a series of 232 radical prostatectomies performed between 1998 and 2001. HOXD3 methylation was significantly greater in GS 7 cancers vs GSr6 cancers (P-value o0.001) as well as pT3/pT4 vs pT2 cancers (P-value o0.001). The proportion of cases with high methylation in GS 7 vs rGS 6 and pT3/pT4 vs pT2 were also significantly different (P-values ¼ 0.002 and 0.005, respectively). There were also significant increases in methylation from Gleason pattern 2-3 and from pattern 3 to 4/5 (paired t-test P-values ¼ 0.01 and o0.001, respectively), whereas methylation from lymph node metastases was decreased when compared with matched tumor tissue (P-value ¼ 0.029). HOXD3 methylation was associated with biochemical recurrence in univariate analysis (P-value ¼ 0.043) and showed evidence for interaction with pathological stage as a predictor variable in Cox regression analysis (P-value ¼ 0.028). The results indicate that HOXD3 methylation distinguishes low-grade prostate cancers from intermediate and high-grade ones and may also have prognostic value when considered together with pathological stage.

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Current practice of Gleason grading of prostate carcinoma

Cited by 54 publications

References 47 publications

BRCA1, BRCA2, AR and IGF-I expression in prostate cancer: Correlation between RT-qPCR and immunohistochemical detection

BRCA1, BRCA2, AR and IGF-I expression in prostate cancer: Correlation between RT-qPCR and immunohistochemical detection

Altered DNA Methylation Landscapes of Polycomb-Repressed Loci Are Associated with Prostate Cancer Progression and ERG Oncogene Expression in Prostate Cancer

DNA methylation of HOXD3 as a marker of prostate cancer progression

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