Topographical analysis of telomere length and correlation with genomic instability in whole mount prostatectomies

• Published in: The Prostate Vol. 71; no. 7; pp. 778 - 790
• Main Authors: Joshua, A.M., Shen, E., Yoshimoto, M., Marrano, P., Zielenska, M., Evans, A.J., Van der Kwast, T., Squire, J.A.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15-05-2011; Wiley-Liss
• Subjects: Biological and medical sciences; Biomarkers, Tumor - metabolism; cancer; Chromosome Aberrations; Chromosomes, Human, Pair 7; Chromosomes, Human, Pair 8; DNA, Neoplasm - analysis; Genomic Instability; Gynecology. Andrology. Obstetrics; Humans; Image Processing, Computer-Assisted; In Situ Hybridization, Fluorescence; Ki-67 Antigen - metabolism; Male; Malondialdehyde - metabolism; Medical sciences; Nephrology. Urinary tract diseases; Oxidative Stress; Prostatectomy; Prostatic Intraepithelial Neoplasia - genetics; Prostatic Intraepithelial Neoplasia - metabolism; Prostatic Intraepithelial Neoplasia - pathology; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Telomere; Andrology; Oxidative stress; Correlation; Nephrology; Gynecology; Malignant tumor; Telomere; Treatment; Length; Surgery; Instability; Prostatectomy; Genome; genomic instability; Cancer
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/pros.21294

BACKGROUND
Many critical events in prostatic carcinogenesis appear to relate to the emergence of genomic instability. Characteristic genomic abnormalities such as 8p loss, 8q gain, trisomy 7, and PTEN microdeletions may provide selective advantages to increase neoplastic transformation. Evidence suggests that telomere dysfunction is a plausible mechanism for some of these abnormalities on the basis of the break‐fusion‐bridge cycle that can lead to manifestations of genomic instability.
METHODS
In this study, we correlate telomere length measured by quantitative FISH in various prostatic histologies with markers of genomic instability and immunohistochemical measures of proliferation and oxidative stress.
RESULTS
We find that telomere shortening is correlated with abnormalities on chromosome 8, but not with trisomy 7 or abnormalities of the PTEN locus. There are associations with C‐MYC aberrations in stroma with greater proximity to cancer and a correlation between telomere length in a number of prostatic histologies and the adjacent stroma, suggesting the importance of microenvironmental effects on telomere maintenance in the prostate. This finding was also supported by the finding of the correlation between telomere attrition and the levels of oxidative stress as measured by malondialdehyde staining in HPIN lesions close to cancer.
CONCLUSIONS
Telomere attrition in the prostate gland is associated with particular genomic aberrations that contribute to the genomic instability characteristic of prostatic carcinogenesis. Correlations between various histologies and adjacent stroma telomere length suggest it is also may reveal microenvironmental effects within the prostate gland. Oxidative stress may contribute to telomere attrition in HPIN close to cancer. Prostate 71:778–790, 2011. © 2010 Wiley‐Liss, Inc.