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Organ‐wide telomeric status in diseased and disease‐free prostatic tissues
Author(s) -
Heaphy Christopher M.,
Fleet Trisha M.,
Treat Eric G.,
Lee SangJoon,
Smith Anthony Y.,
Davis Michael S.,
Griffith Jeffrey K.,
Fischer Edgar G.,
Bisoffi Marco
Publication year - 2010
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21182
Subject(s) - telomere , prostate , hyperplasia , intraepithelial neoplasia , pathology , field cancerization , adenocarcinoma , prostate cancer , cancer , medicine , biology , dna , genetics
Background Telomere attrition occurs early in the development of prostatic adenocarcinoma. However, little is known about either telomere status in benign prostatic hyperplasia (BPH), or the spatial and organ‐wide distribution of potential telomere aberrations throughout all areas of prostatic glands affected by cancer or BPH. Methods Slot blot titration assay was used to determine telomere DNA content (TC), a proxy for telomere length, in macrodissected tissue consisting of 54 normal samples from 5 disease‐free prostates, 128 BPH samples from 4 non‐cancerous prostates, and 45 tumor, 73 BPH, and 4 prostatic intraepithelial neoplasia (PIN) samples from 5 cancerous prostates. Results Compared to TC in normal prostate samples (n = 54; TC mean = 0.98), tumor samples displayed telomere attrition (n = 45; TC mean = 0.67). TC in PIN samples was similar to tumors. TC in BPH samples from cancerous prostates was similar to TC in tumors and also displayed telomere shortening (n = 73; TC mean = 0.76), whereas BPH samples from non‐cancerous prostates displayed longer telomeres (n = 128; TC mean = 1.06). In prostates affected by adenocarcinoma, areas of potential telomere attrition occurred in histologically normal tissues through the entire gland. However, three‐dimensional zoning revealed a pattern of increasing TC as a function of distance from the primary (index) tumor. Conclusions Spatial distributions of TC in prostate specimens indicate a complex “field effect” with varying contributions from both cancer and BPH. The observation that telomere length variations occur in fields of histologically normal tissues surrounding the tumor is of clinical importance, as it may have implications for the diagnosis and focal therapy of prostate cancer. Prostate 70: 1471–1479, 2010. © 2010 Wiley‐Liss, Inc.