DNA Ploidy as Surrogate for Biopsy Gleason Score for Preoperative Organ Versus Nonorgan-confined Prostate Cancer Prediction

Sumit Isharwal, M. Craig Miller, Jonathan Ira Epstein, Leslie A. Mangold, Elizabeth Humphreys, Alan Wayne Partin, Robert W. Veltri

Research output: Contribution to journalArticle

Abstract

Objectives: Transformation of normal epithelium into cancer cells involves epigenetic and genetic changes and modifications in nuclear structure and tissue architecture. To evaluate nuclear morphometric alterations and clinicopathologic features for organ- vs nonorgan-confined prostate carcinoma (PCa) prediction. Methods: Of 557 prospectively enrolled patients, 370 had complete information and sufficient tumor area for all evaluated parameters (281 organ-confined and 89 nonorgan-confined PCa cases). Digital images of Feulgen DNA-stained nuclei were captured from biopsies using the AutoCyte imaging system, and the nuclear morphometric alterations were calculated. Logistic regression analysis with bootstrap resampling was used to determine the factors important for differentiation of the 2 groups and to generate models for organ- vs nonorgan-confined PCa prediction. Results: Several nuclear morphometric features were significantly altered and could differentiate organ- and nonorgan-confined disease. DNA ploidy was the most important factor among the significant nuclear morphometric features and was the second most important factor for organ- vs nonorgan-confined PCa prediction when considered with total prostate-specific antigen (PSA), complexed PSA, free/total PSA, biopsy Gleason score, and clinical stage. The combination of DNA ploidy with clinical stage, total PSA, and biopsy Gleason score showed an improvement of 1.5% in the area under the receiver operator characteristic curves compared with the combination of clinical stage, total PSA, and biopsy Gleason (73.97% vs 72.43%). The use of DNA ploidy in lieu of the biopsy Gleason score in each preoperative model evaluated resulted in equivalent or improved organ- vs nonorgan-confined PCa prediction. Conclusions: The results of our study have shown that DNA ploidy can serve as a surrogate biomarker that has the potential to replace biopsy Gleason scores for organ- vs nonorgan-confined PCa prediction.

Original languageEnglish (US)
Pages (from-to)1092-1097
Number of pages6
JournalUrology
Volume73
Issue number5
DOIs
StatePublished - May 2009

Fingerprint

Neoplasm Grading
Ploidies
Prostate-Specific Antigen
Prostate
Prostatic Neoplasms
Carcinoma
Biopsy
DNA
Epigenomics
Neoplasms
Epithelium
Biomarkers
Logistic Models
Regression Analysis

ASJC Scopus subject areas

  • Urology

Cite this

DNA Ploidy as Surrogate for Biopsy Gleason Score for Preoperative Organ Versus Nonorgan-confined Prostate Cancer Prediction. / Isharwal, Sumit; Miller, M. Craig; Epstein, Jonathan Ira; Mangold, Leslie A.; Humphreys, Elizabeth; Partin, Alan Wayne; Veltri, Robert W.

In: Urology, Vol. 73, No. 5, 05.2009, p. 1092-1097.

Research output: Contribution to journalArticle

Isharwal, Sumit ; Miller, M. Craig ; Epstein, Jonathan Ira ; Mangold, Leslie A. ; Humphreys, Elizabeth ; Partin, Alan Wayne ; Veltri, Robert W. / DNA Ploidy as Surrogate for Biopsy Gleason Score for Preoperative Organ Versus Nonorgan-confined Prostate Cancer Prediction. In: Urology. 2009 ; Vol. 73, No. 5. pp. 1092-1097.
@article{dbfdeaaba64b49728b30169e0425f0d6,
title = "DNA Ploidy as Surrogate for Biopsy Gleason Score for Preoperative Organ Versus Nonorgan-confined Prostate Cancer Prediction",
abstract = "Objectives: Transformation of normal epithelium into cancer cells involves epigenetic and genetic changes and modifications in nuclear structure and tissue architecture. To evaluate nuclear morphometric alterations and clinicopathologic features for organ- vs nonorgan-confined prostate carcinoma (PCa) prediction. Methods: Of 557 prospectively enrolled patients, 370 had complete information and sufficient tumor area for all evaluated parameters (281 organ-confined and 89 nonorgan-confined PCa cases). Digital images of Feulgen DNA-stained nuclei were captured from biopsies using the AutoCyte imaging system, and the nuclear morphometric alterations were calculated. Logistic regression analysis with bootstrap resampling was used to determine the factors important for differentiation of the 2 groups and to generate models for organ- vs nonorgan-confined PCa prediction. Results: Several nuclear morphometric features were significantly altered and could differentiate organ- and nonorgan-confined disease. DNA ploidy was the most important factor among the significant nuclear morphometric features and was the second most important factor for organ- vs nonorgan-confined PCa prediction when considered with total prostate-specific antigen (PSA), complexed PSA, free/total PSA, biopsy Gleason score, and clinical stage. The combination of DNA ploidy with clinical stage, total PSA, and biopsy Gleason score showed an improvement of 1.5{\%} in the area under the receiver operator characteristic curves compared with the combination of clinical stage, total PSA, and biopsy Gleason (73.97{\%} vs 72.43{\%}). The use of DNA ploidy in lieu of the biopsy Gleason score in each preoperative model evaluated resulted in equivalent or improved organ- vs nonorgan-confined PCa prediction. Conclusions: The results of our study have shown that DNA ploidy can serve as a surrogate biomarker that has the potential to replace biopsy Gleason scores for organ- vs nonorgan-confined PCa prediction.",
author = "Sumit Isharwal and Miller, {M. Craig} and Epstein, {Jonathan Ira} and Mangold, {Leslie A.} and Elizabeth Humphreys and Partin, {Alan Wayne} and Veltri, {Robert W.}",
year = "2009",
month = "5",
doi = "10.1016/j.urology.2008.09.060",
language = "English (US)",
volume = "73",
pages = "1092--1097",
journal = "Urology",
issn = "0090-4295",
publisher = "Elsevier Inc.",
number = "5",

}

TY - JOUR

T1 - DNA Ploidy as Surrogate for Biopsy Gleason Score for Preoperative Organ Versus Nonorgan-confined Prostate Cancer Prediction

AU - Isharwal, Sumit

AU - Miller, M. Craig

AU - Epstein, Jonathan Ira

AU - Mangold, Leslie A.

AU - Humphreys, Elizabeth

AU - Partin, Alan Wayne

AU - Veltri, Robert W.

PY - 2009/5

Y1 - 2009/5

N2 - Objectives: Transformation of normal epithelium into cancer cells involves epigenetic and genetic changes and modifications in nuclear structure and tissue architecture. To evaluate nuclear morphometric alterations and clinicopathologic features for organ- vs nonorgan-confined prostate carcinoma (PCa) prediction. Methods: Of 557 prospectively enrolled patients, 370 had complete information and sufficient tumor area for all evaluated parameters (281 organ-confined and 89 nonorgan-confined PCa cases). Digital images of Feulgen DNA-stained nuclei were captured from biopsies using the AutoCyte imaging system, and the nuclear morphometric alterations were calculated. Logistic regression analysis with bootstrap resampling was used to determine the factors important for differentiation of the 2 groups and to generate models for organ- vs nonorgan-confined PCa prediction. Results: Several nuclear morphometric features were significantly altered and could differentiate organ- and nonorgan-confined disease. DNA ploidy was the most important factor among the significant nuclear morphometric features and was the second most important factor for organ- vs nonorgan-confined PCa prediction when considered with total prostate-specific antigen (PSA), complexed PSA, free/total PSA, biopsy Gleason score, and clinical stage. The combination of DNA ploidy with clinical stage, total PSA, and biopsy Gleason score showed an improvement of 1.5% in the area under the receiver operator characteristic curves compared with the combination of clinical stage, total PSA, and biopsy Gleason (73.97% vs 72.43%). The use of DNA ploidy in lieu of the biopsy Gleason score in each preoperative model evaluated resulted in equivalent or improved organ- vs nonorgan-confined PCa prediction. Conclusions: The results of our study have shown that DNA ploidy can serve as a surrogate biomarker that has the potential to replace biopsy Gleason scores for organ- vs nonorgan-confined PCa prediction.

AB - Objectives: Transformation of normal epithelium into cancer cells involves epigenetic and genetic changes and modifications in nuclear structure and tissue architecture. To evaluate nuclear morphometric alterations and clinicopathologic features for organ- vs nonorgan-confined prostate carcinoma (PCa) prediction. Methods: Of 557 prospectively enrolled patients, 370 had complete information and sufficient tumor area for all evaluated parameters (281 organ-confined and 89 nonorgan-confined PCa cases). Digital images of Feulgen DNA-stained nuclei were captured from biopsies using the AutoCyte imaging system, and the nuclear morphometric alterations were calculated. Logistic regression analysis with bootstrap resampling was used to determine the factors important for differentiation of the 2 groups and to generate models for organ- vs nonorgan-confined PCa prediction. Results: Several nuclear morphometric features were significantly altered and could differentiate organ- and nonorgan-confined disease. DNA ploidy was the most important factor among the significant nuclear morphometric features and was the second most important factor for organ- vs nonorgan-confined PCa prediction when considered with total prostate-specific antigen (PSA), complexed PSA, free/total PSA, biopsy Gleason score, and clinical stage. The combination of DNA ploidy with clinical stage, total PSA, and biopsy Gleason score showed an improvement of 1.5% in the area under the receiver operator characteristic curves compared with the combination of clinical stage, total PSA, and biopsy Gleason (73.97% vs 72.43%). The use of DNA ploidy in lieu of the biopsy Gleason score in each preoperative model evaluated resulted in equivalent or improved organ- vs nonorgan-confined PCa prediction. Conclusions: The results of our study have shown that DNA ploidy can serve as a surrogate biomarker that has the potential to replace biopsy Gleason scores for organ- vs nonorgan-confined PCa prediction.

UR - http://www.scopus.com/inward/record.url?scp=65049086764&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=65049086764&partnerID=8YFLogxK

U2 - 10.1016/j.urology.2008.09.060

DO - 10.1016/j.urology.2008.09.060

M3 - Article

C2 - 19193410

AN - SCOPUS:65049086764

VL - 73

SP - 1092

EP - 1097

JO - Urology

JF - Urology

SN - 0090-4295

IS - 5

ER -