Quantitative Analysis of ERG Expression and Its Splice Isoforms in Formalin-Fixed, Paraffin-Embedded Prostate Cancer Samples
Autor: | Michael Ladomery, David Gillatt, Jonathan Aning, Raj Persad, Saima Karamat, Rachel M. Hagen, Jon Oxley, Anthony Rhodes, Patricia Adamo |
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Rok vydání: | 2014 |
Předmět: |
PCA3
Biochemical recurrence genetic structures medicine.diagnostic_test General Medicine Biology medicine.disease Molecular biology eye diseases Reverse transcription polymerase chain reaction Exon Prostate cancer Real-time polymerase chain reaction medicine.anatomical_structure Prostate medicine sense organs Fluorescence in situ hybridization |
Zdroj: | American Journal of Clinical Pathology. 142:533-540 |
ISSN: | 1943-7722 0002-9173 |
Popis: | Objectives: The proto-oncogene ETS-related gene ( ERG ) is consistently overexpressed in prostate cancer. Alternatively spliced isoforms of ERG have variable biological activities; inclusion of exon 11 (72 base pairs [bp]) is associated with aggressiveness and progression of disease. Exon 10 (81 bp) has also been shown to be alternatively spliced. Within this study, we assess whether ERG protein, messenger RNA (mRNA), and ERG splice isoform mRNA expression is altered as prostate cancer progresses. Methods: Detection of the TMPRSS2-ERG fusion was done using direct methods (reverse transcription polymerase chain reaction [PCR] and fluorescence in situ hybridization) and indirect methods for ERG mRNA and protein expression using quantitative PCR and immunohistochemistry, respectively. A linear equation method was used to quantitatively determine relative proportions of ERG variants ( ERG72/Δ72 , ERG81/Δ81 ) for each sample. Results: ERG mRNA and protein expression is increased in patients with advanced prostate cancer, with higher levels of ERG expression significantly associated with seminal vesicle invasion (stage pT3b) and biochemical recurrence. Genes involved in cell migration and invasiveness (matrix metalloproteinase 7, osteopontin, and septin 9) are increased in prostate cancers that overexpress ERG . In addition, there is a clear indication of increased retention of exons 10 and 11 in prostate cancer. Conclusions: Analysis of ERG and its variants may be valuable in determining prognosis and development of prostate cancer. |
Databáze: | OpenAIRE |
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