INDIGO Home University of Illinois at Urbana-Champaign logo uic building uic pavilion uic student center

Development of a Nuclear Morphometric Signature for Prostate Cancer Risk in Negative Biopsies

Show full item record

Bookmark or cite this item:

Files in this item

File Description Format
PDF journal.pone.0069457.pdf (1MB) Main Article PDF
Title: Development of a Nuclear Morphometric Signature for Prostate Cancer Risk in Negative Biopsies
Author(s): Gann, Peter H.; Deaton, Ryan; Amatya, Anup; Mohnani, Mahesh; Rueter, Erika Enk; Yang, Yirong; Ananthanarayanan, Viju
Abstract: BACKGROUND: Our objective was to develop and validate a multi-feature nuclear score based on image analysis of direct DNA staining, and to test its association with field effects and subsequent detection of prostate cancer (PCa) in benign biopsies. METHODS: Tissue sections from 39 prostatectomies were Feulgen-stained and digitally scanned (400×), providing maps of DNA content per pixel. PCa and benign epithelial nuclei were randomly selected for measurement of 52 basic morphometric features. Logistic regression models discriminating benign from PCa nuclei, and benign from malignant nuclear populations, were built and cross-validated by AUC analysis. Nuclear populations were randomly collected <1 mm or >5 mm from cancer foci, and from cancer-free prostates, HGPIN, and PCa Gleason grade 3-5. Nuclei also were collected from negative biopsy subjects who had a subsequent diagnosis of PCa and age-matched cancer-free controls (20 pairs). RESULTS: A multi-feature nuclear score discriminated cancer from benign cell populations with AUCs of 0.91 and 0.79, respectively, in training and validation sets of patients. In prostatectomy samples, both nuclear- and population-level models revealed cancer-like features in benign nuclei adjacent to PCa, compared to nuclei that were more distant or from PCa-free glands. In negative biopsies, a validated model with 5 variance features yielded significantly higher scores in cases than controls (P = 0.026). CONCLUSIONS: A multifeature nuclear morphometric score, obtained by automated digital analysis, was validated for discrimination of benign from cancer nuclei. This score demonstrated field effects in benign epithelial nuclei at varying distance from PCa lesions, and was associated with subsequent PCa detection in negative biopsies. IMPACT: This nuclear score shows promise as a risk predictor among men with negative biopsies and as an intermediate biomarker in Phase II chemoprevention trials. The results also suggest that subvisual disturbances in nuclear structure precede the development of pre-neoplastic lesions.
Issue Date: 2013-07
Publisher: PLoS One
Citation Info: Gann PH, Deaton R, Amatya A, Mohnani M, Rueter EE, et al. (2013) Development of a Nuclear Morphometric Signature for Prostate Cancer Risk in Negative Biopsies. PLoS ONE 8(7): e69457. doi:10.1371/journal.pone.0069457
Type: Article
Description: © 2013 Gann et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. © 2013 by Public Library of Science, PLoS ONE
ISSN: 1932-6203
Sponsor: Supported by grants from the National Institutes of Health/National Cancer Institute RO1 CA155301 and RO1 CA90759.
Date Available in INDIGO: 2014-01-09

This item appears in the following Collection(s)

Show full item record


Country Code Views
United States of America 311
China 66
Russian Federation 36
Ukraine 11
Germany 10


My Account


Access Key