PTEN losses exhibit heterogeneity in multifocal prostatic adenocarcinoma and are associated with higher Gleason grade

Prostatic adenocarcinoma is an epithelial malignancy characterized by marked histological heterogeneity. It most often has a multifocal distribution within the gland, and different Gleason grades may be present within different foci. Data from our group and others have shown that the genomic deletio...

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Bibliographic Details
Published in:Modern pathology 2013-03, Vol.26 (3), p.435-447
Main Authors: Yoshimoto, Maisa, Ding, Keyue, Sweet, Joan M, Ludkovski, Olga, Trottier, Greg, Song, Kyu S, Joshua, Anthony M, E Fleshner, Neil, Squire, Jeremy A, Evans, Andrew J
Format: Article
Language:English
Subjects:
Adenocarcinoma - enzymology
Adenocarcinoma - genetics
Adenocarcinoma - pathology
Adenocarcinoma - surgery
Adult
Aged
Biomarkers, Tumor - analysis
Biomarkers, Tumor - genetics
Biopsy
Biopsy, Large-Core Needle
Chi-Square Distribution
Clinical trials
Down-Regulation
Genetic Predisposition to Disease
genomic biomarkers
Health care networks
histologic heterogeneity
Hospitals
Humans
In Situ Hybridization, Fluorescence
index tumor
Male
Medical prognosis
Middle Aged
Neoplasm Grading
Neoplasms, Multiple Primary - enzymology
Neoplasms, Multiple Primary - genetics
Neoplasms, Multiple Primary - pathology
Neoplasms, Multiple Primary - surgery
Oncogene Proteins, Fusion - genetics
Oncology
Pathology
Phenotype
Phosphatase
prognosis
Prostate cancer
Prostatectomy
Prostatic Neoplasms - enzymology
Prostatic Neoplasms - genetics
Prostatic Neoplasms - pathology
Prostatic Neoplasms - surgery
PTEN gene
PTEN Phosphohydrolase - analysis
PTEN Phosphohydrolase - genetics
Tissue Array Analysis
TMPRSS2–ERG fusion
Treatment Outcome
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Summary:Prostatic adenocarcinoma is an epithelial malignancy characterized by marked histological heterogeneity. It most often has a multifocal distribution within the gland, and different Gleason grades may be present within different foci. Data from our group and others have shown that the genomic deletion of the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) tumor suppressor gene and the disruption of the ETS gene family have a central role in prostate cancer and are likely to be associated with Gleason grade. In this study, prostate cancer samples were systematically analyzed to determine whether there was concordance between PTEN losses and TMPRSS2–ERG fusion rearrangements, within or between foci in multifocal disease, using well-annotated tissue microarrays (TMAs) consisting of 724 cores derived from 142 radical prostatectomy specimens. Three-color fluorescence in situ hybridization analysis of both the PTEN deletion and the TMPRSS2–ERG fusion was used to precisely map genetic heterogeneity, both within and between tumor foci represented on the TMA. PTEN deletion was observed in 56 of 134 (42%) patients (hemizygous=42 and homozygous=14). TMPRSS2–ERG fusion was observed in 63 of 139 (45%) patients. When analyzed by Gleason pattern for a given TMA core, PTEN deletions were significantly associated with Gleason grades 4 or 5 over grade 3 (P
ISSN:0893-3952
1530-0285
DOI:10.1038/modpathol.2012.162