Cellular and Molecular Pathology of Prostate Cancer Precursors

Foster, Christopher S.; Bostwick, David G.; Bonkhoff, Helmut; Damber, Jan‐Erik; Kwast, Theo van der; Montironi, R; Sakr, W. A.

doi:10.1080/003655900750169284

Cited by 70 publications

(42 citation statements)

References 101 publications

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“…Interestingly, a more detailed Q-FISH analysis of four different HPIN foci on a subset of CaP patients (not shown) displayed a high degree of variability in centromere and telomere intensities between individual foci. This observation is also in keeping with the multifocal model of CaP oncogenesis (Bostwick et al, 1998;Foster et al, 2000;Harding and Theodorescu, 2000).…”

Section: Discussionsupporting

confidence: 57%

Evidence of multifocality of telomere erosion in high-grade prostatic intraepithelial neoplasia (HPIN) and concurrent carcinoma

et al. 2003

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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.

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Section: Discussionsupporting

confidence: 57%

Evidence of multifocality of telomere erosion in high-grade prostatic intraepithelial neoplasia (HPIN) and concurrent carcinoma

et al. 2003

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“…Reassignment of areas of 'cancer' or 'normal' in each core was carried out on the basis of histopathological examination of haematoxylin and eosin and p63/AMACR-stained sections that flanked the TMA slice used for FISH studies. The morphological criteria for selection of 'normal' and 'malignant' prostatic epithelium conformed to previously published definitions (Foster, 2000;Foster et al, 2000Foster et al, , 2004 . 'Hyperplasia', 'dysplasia' and 'PIN' were not scored in this study.…”

Section: Tissue Microarraysmentioning

confidence: 86%

Duplication of the fusion of TMPRSS2 to ERG sequences identifies fatal human prostate cancer

Clark²,

et al. 2007

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New predictive markers for managing prostate cancer are urgently required because of the highly variable natural history of this disease. At the time of diagnosis, Gleason score provides the gold standard for assessing the aggressiveness of prostate cancer. However, the recent discovery of TMPRSS2 fusions to the ERG gene in prostate cancer raises the possibility of using alterations at the ERG locus as additional mechanism-based prognostic indicators. Fluorescence in situ hybridization (FISH) assays were used to assess ERG gene status in a cohort of 445 prostate cancers from patients who had been conservatively managed. The FISH assays detected separation of 5 0 (labelled green) and 3 0 (labelled red) ERG sequences, which is a consequence of the TMPRSS2-ERG fusion, and additionally identify interstitial deletion of genomic sequences between the tandemly located TMPRSS2 and ERG gene sequences on chromosome 21. Cancers lacking ERG alterations exhibited favourable cause-specific survival (90% survival at 8 years). We identify a novel category of prostate cancers, characterized by duplication of the fusion of TMPRSS2 to ERG sequences together with interstitial deletion of sequences 5 0 to ERG (called '2 þ Edel'), which by comparison exhibited extremely poor cause-specific survival (hazard ratio ¼ 6.10, 95% confidence ratio ¼ 3.33-11.15, Po0.001, 25% survival at 8 years). In multivariate analysis, '2 þ Edel' provided significant prognostic information (P ¼ 0.003) in addition to that provided by Gleason score and prostate-specific antigen level at diagnosis. Other individual categories of ERG alteration were associated with intermediate or good prognosis. We conclude that determination of ERG gene status, including duplication of the fusion of TMPRSS2 to ERG sequences in 2 þ Edel, allows stratification of prostate cancer into distinct survival categories.

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“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] PIN is the abnormal proliferation within the prostatic ducts, ductules, and large acini of premalignant foci of cellular dysplasia and carcinoma in situ without stromal invasion. [18][19][20] The diagnostic term 'prostatic intraepithelial neoplasia' has been endorsed at multiple multidisciplinary and pathology consensus meetings, 6,14,[21][22][23][24] and the interobserver agreement between pathologists has been determined to be 'good to excellent' 25,26 for high-grade PIN.…”

Section: High-grade Prostatic Intraepithelial Neoplasia (Pin)mentioning

confidence: 99%

High-grade prostatic intraepithelial neoplasia

2004

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High-grade prostatic intraepithelial neoplasia (PIN) is now accepted as the most likely preinvasive stage of adenocarcinoma, almost two decades after its first formal description. PIN has a high predictive value as a marker for adenocarcinoma, and its identification warrants repeat biopsy for concurrent or subsequent invasive carcinoma. The only method of detection is biopsy; PIN does not significantly elevate serum prostate-specific antigen (PSA) concentration or its derivatives and cannot be detected by current imaging techniques, including ultrasound. Most patients with PIN will develop carcinoma within 10 years. PIN is associated with progressive abnormalities of phenotype and genotype, which are similar to cancer rather than normal prostatic epithelium, indicating impairment of cell differentiation with advancing stages of prostatic carcinogenesis. Androgen deprivation therapy decreases the prevalence and extent of PIN, suggesting that this form of treatment may play a role in chemoprevention.

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Cellular and Molecular Pathology of Prostate Cancer Precursors

Cited by 70 publications

References 101 publications

Evidence of multifocality of telomere erosion in high-grade prostatic intraepithelial neoplasia (HPIN) and concurrent carcinoma

Evidence of multifocality of telomere erosion in high-grade prostatic intraepithelial neoplasia (HPIN) and concurrent carcinoma

Duplication of the fusion of TMPRSS2 to ERG sequences identifies fatal human prostate cancer

High-grade prostatic intraepithelial neoplasia

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