title: Evidence of multifocality of telomere erosion in high-grade prostatic intraepithelial neoplasia (HPIN) and concurrent carcinoma.
abstract: Mechanisms underlying prostate cancer (CaP) initiation and progression are poorly understood. A chromosomal instability mechanism leading to the generation of numerical and structural chromosomal changes has been implicated in the preneoplastic and neoplastic stages of CaP. Telomere dysfunction is one potential mechanism associated with the onset of such instability. To determine whether there was alteration in telomere length and chromosome number, 15 paraffin-embedded prostatectomy specimens were investigated using quantitative peptide nucleic acid (PNA) FISH analysis of representative foci of carcinoma, putative precancerous lesions (high-grade prostatic intraepithelial neoplasia, HPIN) and nondysplastic prostate epithelium. A significant decrease in telomere length was shown in both HPIN and CaP in comparison with normal epithelium. In addition, elevated rates of aneusomy suggested that increased levels of chromosomal aberrations were associated with decreased telomere length. Moreover, multiple foci of HPIN were shown to have a heterogeneous overall reduction of telomere length. This reduction was more evident in the histologic regions of the prostate containing CaP. Such observations lend support to the hypothesis that telomere erosion may be a consistent feature of CaP oncogenesis and may also be associated with the generation of chromosomal instability that characterizes this malignancy.
authors.affiliation: Ontario Cancer Institute/Princess Margaret Hospital, The University Health Network, Toronto, Canada.
authors.forename: Bisera
authors.initials: B
authors.lastname: Vukovic
authors.forename: Paul C
authors.initials: PC
authors.lastname: Park
authors.forename: Jaudah
authors.initials: J
authors.lastname: Al-Maghrabi
authors.forename: Ben
authors.initials: B
authors.lastname: Beheshti
authors.forename: Joan
authors.initials: J
authors.lastname: Sweet
authors.forename: Andy
authors.initials: A
authors.lastname: Evans
authors.forename: John
authors.initials: J
authors.lastname: Trachtenberg
authors.forename: Jeremy
authors.initials: J
authors.lastname: Squire
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry / Q000235:genetics* / Q000648:ultrastructure; D000368:Aged; D000375:Aging / Q000235:genetics; D000782:Aneuploidy; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002869:Chromosome Aberrations; D018450:Disease Progression; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D016612:Paraffin Embedding; D019048:Prostatic Intraepithelial Neoplasia / Q000737:chemistry / Q000235:genetics* / Q000648:ultrastructure; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000648:ultrastructure; D016615:Telomere / Q000648:ultrastructure*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53