A dna cytometric proliferation index improves the value of the dna ploidy pattern as a prognosticating tool in patients with carcinoma of the prostate

Ahlgren, Göran; Lindholm, Karin; Falkmer, Sture; Abrahamsson, Per‐Anders

doi:10.1016/s0090-4295(97)00223-9

Cited by 17 publications

(16 citation statements)

References 16 publications

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“…Therefore, our statistical power to detect a significant association between the amount of tumor in the block and DNA ploidy in the subset of tetraploid and aneuploid cases was limited. Proliferation as a prognostic marker in prostate cancer, although less well defined, has also been shown to be a marker for outcome (22,(37)(38)(39). We wanted to investigate what, if any, impact the above-noted histologic features had on the proliferation indices (%S and %S ϩ %G2M) quantified by FCM.…”

Section: Discussionmentioning

confidence: 99%

Factors That Influence the Measurement of Prostate Cancer DNA Ploidy and Proliferation in Paraffin Embedded Tissue Evaluated by Flow Cytometry

Cheville

Katzmann

et al. 2001

Modern Pathology

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DNA ploidy (1-6) and proliferation (7,8) have been shown to provide prognostic information for prostate cancer. Studies examining the relationship between ploidy and proliferation and patient outcome are often based upon flow cytometry (FCM) data using formalin-fixed, paraffin-embedded tissue from radical retropubic prostatectomy (RRP) specimens. However, FCM cannot readily distinguish among benign epithelial, stromal, and inflammatory cells, high grade prostatic intraepithelial neoplasia (HGPIN), and cancer cells. Furthermore, studies that do not show DNA ploidy and proliferation as independent prognostic markers emphasize the strong correlation of cancer Gleason score with DNA ploidy and proliferation (9 -11).To the best of our knowledge, there are no published reports directly assessing the degree to which non-invasive tumor components in paraffinembedded tissue blocks are associated with prostate cancer ploidy and proliferation results determined by FCM. In this study, we evaluated hematoxylin and eosin (H&E) histologic features from 322 RRP formalin-fixed, paraffin-embedded tissue specimens used for determining DNA ploidy,

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Section: Discussionmentioning

confidence: 99%

Factors That Influence the Measurement of Prostate Cancer DNA Ploidy and Proliferation in Paraffin Embedded Tissue Evaluated by Flow Cytometry

Cheville

Katzmann

et al. 2001

Modern Pathology

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“…While [168,228] and [230] found discrepancies in only 3.8%, 5.0% and 8.0%, [210,232] reported different ploidy-levels in 24.1% and 29.0%. These figures are lower than comparable ones for the Gleason-score (30%:11).…”

Section: Heterogeneitymentioning

confidence: 93%

“…4 level 3b studies do the same [190,202,203], 1 of them univariate [204]. 6 studies provided a significant correlation of DNA-ploidy with overall survival after hormonal therapy in a multivariate design [169,[208][209][210][211]213]. 6 level 3b-studies [85], 7 of them multivariate, showed the same [110,169,[214][215][216][217].…”

Section: Methodologically Sufficient Papersmentioning

confidence: 99%

“…Thus, concerning diploidy vs. non-diploidy, it is not relevant which c-value the peridiploid peak exactly has, but if there is a second peak at 4c or elsewhere. According to [210,234] a prognostically relevant proliferation rate >5% can be stated in peridiploid DNA-histograms, supposed a reasonable number of >1000 of nuclei had been measured to obtain representative results [34].…”

Section: Shortcomings Of Published Papersmentioning

confidence: 99%

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DNA-cytometric grading of prostate cancer Systematic review with descriptive data analysis

Böcking¹,

Tils²,

Schramm³

et al. 2014

Pathol Discov

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Gleason-score <=6, assessed on core needle biopsies, is an essential prognostic parameter to offer the strategy of Active Surveillance (AS) to patients with locally confined cancers of the prostate. Yet, its interobserver reproducibility is low (48-70%) and its prognostic validity unsatisfactory. An option to complementary assess the malignant potential of these cancers are objective DNA-ploidy-measurements on existing biopsies. For that purpose chromosomal heterogeneity is indirectly quantified by DNA-cytometry resulting in DNA-grades of malignancy 1-4. This review systematically trawls and evaluates all scientific publications on the potential diagnostic and prognostic validity and the heterogeneity of DNA-ploidy measurements in cancers of the prostate between 1966 and 2013. Publications have been classified into Oxford levels of evidence and levels of significance were given for the correlation of DNA-ploidy with different clinical outcomes. 114 scientific articles had to be excluded because of different methodological reasons. All but one of the 67 methodologically acceptable articles report on a significant diagnostic resp. prognostic significance of DNA ploidy measurements in cancers of the prostate. 8 level 1b studies report that DNA-ploidy, assessed on punch biopsies independently predicts organ confinement as assessed after radical prostatectomy. 18 level 2b studies prove that DNA-ploidy measurements add statistically significant information to the Gleason-score. 16 level 2b investigations report a significant correlation of DNA-ploidy with recurrence-free survival. 15 level 2b studies document a significant correlation with overall survival after different types of therapy. 5 level 2b investigations prove a significant correlation with local recurrence or progress after radical prostatectomy. 3 level 2b publications show a significant correlation of DNAploidy with the occurrence of lymph node-or bone metastases after radical prostatectomy. 1 level 2b study documents the additional prognostic value of DNA-ploidy measurements over conventional subjective grading in prostate cancer patients under AS. All existing 15 narrative reviews on selected articles dealing with prognostic DNA-cytometry in cancers of the prostate are in favor of this method. Prospective level 1b studies, especially those proving the validity of DNA ploidy measurements to predict non-progression in patients with clinically insignificant low-grade low stage cancers of the prostate eligible for Active Surveillance additionally to the Gleason-score are still missing.

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“…Cells in the late G1 and S phase show strong nuclear staining, which is not detected in mitotic or arrested cells. In prostate carcinoma the proliferative activity has been related to disease progression (3) and risk of death (4) and has been used to demonstrate highgrade prostatic intraepithelial neoplasia (HG-PIN) as a precursor of the invasive carcinoma (5). p53 is a tumor suppressor gene important in cell cycle control, DNA repair and apoptosis (6).…”

Section: Introductionmentioning

confidence: 99%

Analysis of p53 expression and proliferative assessment using PCNA in localized prostate carcinoma

Leite

Srougi

Nesralhah

et al. 1999

Braz J Med Biol Res

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The surgical specimens from 51 men submitted to radical prostatectomy for localized prostate cancer were examined by immunohistochemistry using proliferation cell nuclear antigen (PCNA) monoclonal antibody to evaluate the proliferative index (PI). The relationship between PI, biological variables and p53 protein expression was evaluated by immunohistochemistry. PI was low in invasive localized prostate carcinoma (mean, 12.4%) and the incidence of PCNA-positive cells was significantly higher in tumors with p53 expression (P = 0.0226). There was no statistical difference in PCNA values when biological parameters such as Gleason score, tumor volume, extraprostatic involvement, seminal vesicle infiltration or lymph node metastasis were considered. We conclude that proliferative activity is usually low in prostate carcinoma but is correlated with p53 immune staining, indicating that p53 is important in cell cycle control in this neoplasm.

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A dna cytometric proliferation index improves the value of the dna ploidy pattern as a prognosticating tool in patients with carcinoma of the prostate

Cited by 17 publications

References 16 publications

Factors That Influence the Measurement of Prostate Cancer DNA Ploidy and Proliferation in Paraffin Embedded Tissue Evaluated by Flow Cytometry

Factors That Influence the Measurement of Prostate Cancer DNA Ploidy and Proliferation in Paraffin Embedded Tissue Evaluated by Flow Cytometry

DNA-cytometric grading of prostate cancer Systematic review with descriptive data analysis

Analysis of p53 expression and proliferative assessment using PCNA in localized prostate carcinoma

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