Stage B Prostate Cancer: Correlation of DNA Ploidy Analysis with Histological and Clinical Parameters

Abstract

BACKGROUND: The ability to accurately predict tumor behavior and patient survival is a problem in managing patients with prostate cancer. Prognostic variables in predicting death from tumor include prostate-specific antigen (PSA) level, histological grade, and clinical stage. Observer subjectivity is inherent in determining grade and stage; thus, criteria that are more objective are needed to identify patients for appropriate treatment. METHODS: The authors correlated flow cytometric nuclear DNA ploidy with Gleason score, PSA level, and recurrence risk in patients who underwent radical retropubic prostatectomy and bilateral pelvic lymphadenectomy between 1987 and 1993 for histopathologic stage B prostate cancer (T2, N0, M0). RESULTS: Of the tumors analyzed, 64% were DNA diploid with a low proliferative fraction, 25% were DNA diploid with a high proliferative fraction, and 11% were DNA aneuploid. DNA aneuploidy was associated with high Gleason grade (7-10). All Gleason grade 10 tumors were DNA aneuploid. Both DNA aneuploidy and high proliferative fraction (S+G2M) were statistically correlated with high Gleason grade and adverse prognosis but not with PSA level or patient age. CONCLUSIONS: A direct relationship is shown between both DNA aneuploidy and a high proliferation index with aggressive biological behavior in stage B prostatic cancer. Objective tumor criteria are needed to choose treatment more selectively for individual patients.

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

“…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.…”

Cancer Biomarker Discovery: The Entropic Hallmark

“…“ In sum, cancer is caused by chromosomal disorganization, which increases karyotypic entropy ” [601]. Regarding the cancer types studied in this paper, one particular “measure of disorder of a system”, aneuploidy , has been observed in poorly-differentiated prostate cancer cells and it is often associated with a more agreessive phenotype [602], [603], increased PSA levels [604], [605], and correlate with Gleason score [606], [607], [608]. Gene fusions and chromosomal rearrangements are other source of increase in the “disorder” of the genome organization and they are increasingly being recognized as a major player in prostate cancer progression [609].…”

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

“…9 level 3b studies report the same after radical prostatectomy [167,170,184, • 5 level 2b studies [170,180,182,190,225] report a significant correlation between DNA-ploidy parameters and the occurrence of local progression or recurrence after radical prostatectomy, 1 after hormonal therapy [234], 1 after brachytherapy [227] ( Table 7).…”

“…• 6 level 2b studies proved a significant correlation of DNAploidy with overall survival after radical prostatectomy [180,200], 2 of them in a multivariate design [178,198,199,201]. 4 level 3b studies do the same [190,202,203], 1 of them univariate [204].…”

“…• 10 level 2b studies were found that report on a statistically significant correlation of DNA-cytometric features with recurrence-free survival after radical prostatectomy in a multivariate-analysis [16,175- an univariate analysis [180,182,183] Table 4. [193] found the same after external radiation in a multivariate analysis.…”