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. 2014:773:77-99.
doi: 10.1007/978-1-4899-8032-8_4.

Nuclear morphometry, epigenetic changes, and clinical relevance in prostate cancer

Affiliations

Nuclear morphometry, epigenetic changes, and clinical relevance in prostate cancer

Robert W Veltri et al. Adv Exp Med Biol. 2014.

Abstract

Nuclear structure alterations in cancer involve global genetic (mutations, amplifications, copy number variations, translocations, etc.) and epigenetic (DNA methylation and histone modifications) events that dramatically and dynamically spatially change chromatin, nuclear body, and chromosome organization. In prostate cancer (CaP) there appears to be early (<50 years) versus late (>60 years) onset clinically significant cancers, and we have yet to clearly understand the hereditary and somatic-based molecular pathways involved. We do know that once cancer is initiated, dedifferentiation of the prostate gland occurs with significant changes in nuclear structure driven by numerous genetic and epigenetic processes. This review focuses upon the nuclear architecture and epigenetic dynamics with potential translational clinically relevant applications to CaP. Further, the review correlates changes in the cancer-driven epigenetic process at the molecular level and correlates these alterations to nuclear morphological quantitative measurements. Finally, we address how we can best utilize this knowledge to improve the efficacy of personalized treatment of cancer.

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Figures

Fig. 1
Fig. 1
Automated analysis of nuclear pathology in prostate cancer (a) General Description of the AutoCyte Pathology Workstation’s operation. (b) Images of single 2D Feulgen stained prostate benign, high grade prostate intraepithelial neoplasia (HGPIN), and prostate cancer nuclei (left to right, upper panels). These blue colored epithelial nuclei are captured by the APW software (QUIV DNA) and 40 nuclear morphometric descriptors (NMDs) are used to calculated image-based solutions for CaP outcomes. In the bottom panel is a 3D construction of the nuclear pixel grey level map (made using Mathcad) shows variations in nuclear chromatin labeled with the Feulgen DNA stain
Fig. 2
Fig. 2
Statistical contribution of nuclear morphometry in predicting prostate cancer. Bar graph of the statistical contribution of nuclear morphometry (a) and clinical pathological features combined with morphometry (b) based on boot strapping (200×) a cox proportional hazards model analysis to predict organ-confined prostate cancer. Notably DNA Ploidy is retained in a multivariate prediction model for organ-confined PCa
Fig. 3
Fig. 3
This figure demonstrates how AdACM computer-assisted image analysis can separate Gleason grade pattern 3 from 4. The graph in the upper right panel shows how three features can accurately separate 3 from 4 (Odds Ratio = 0.90). In the top left hand panel of the figure, the segmentation method is described. In the bottom right panel of the figure, the plot depicts the contribution of nuclear morphology, architecture, and texture to the computational solution plot in the upper right hand space
Fig. 4
Fig. 4
Epigenetic marks involved in tumorigenesis. The illustration shows the interaction of Polycomb 2 transcription complex with the nucleosome transcription complex as well as sites for modification of the histones

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References

    1. Virchow R. Cellular pathology as based upon physiological and pathological histology. Philadelphia, PA: J B Lippincott; 1863. - PubMed
    1. Beale L. Examination of sputum from a case of cancer of the pharynx and the adjacent parts. Arch Med (Lond) 1860;2:44–46.
    1. Long SR, Cohen MB. Classics in cytology. VI: the early cytologic discoveries of Lionel S. Beale. Diagn Cytopathol. 1993;9(5):595–598. - PubMed
    1. Cremer T, Cremer C. Rise, fall and resurrection of chromosome territories: a historical perspective. Part II. Fall and resurrection of chromosome territories during the 1950s to 1980s. Part III. Chromosome territories and the functional nuclear architecture: experiments and models from the 1990s to the present. Eur J Histochem. 2006;50(4):223–272. - PubMed
    1. Cremer T, Cremer C. Rise, fall and resurrection of chromosome territories: a historical perspective. Part I. The rise of chromosome territories. Eur J Histochem. 2006;50(3):161–176. - PubMed