Evaluation of PTEN and TMPRSS2-ERG Abnormalities in Prostate Cancer by FISH and Immunohistochemistry To Address Intra- and Inter-Tissue Heterogeneity and Disease Progression.
Anthony M Joshua, Andrew Evans, Jeremy Squire, Maisa Yoshimoto, Olga Ludkovski, Shyh-Han Tan, Albert Dobi, Bungo Furusato, Gyorgy Petrovics, Shiv Srivastava, Isabell A Sesterhenn. University of Toronto, ON, Canada; Toronto General Hospital, ON, Canada; Queens University, Kingston, ON, Canada; USUHS, Rockville, MD; Armed Forces Institute of Pathology, Washington, DC
Background: Gene fusions involving the ERG oncogene and deletions of the PTEN tumor suppressor gene are frequent alterations in prostate cancer. Recent reports highlighted the cooperation of these two pathways in prostate cancer progression using mouse models. Our laboratory developed a specific monoclonal antibody (ERG MAb) recognizing the ERG oncoprotein in human prostate tissue. The objective of this study was to determine the frequency of ERG positive prostate cancer by immunohistochemistry (IHC) compared to ERG gene fusion frequency by fluorescent in situ hybridization (FISH), their association with PTEN deletion, and correlation with clinico-pathological parameters of disease progression.
Design: A tissue microarray (TMA) was constructed from 142 radical prostatectomy (RP) specimens with usual acinar-type prostate carcinoma obtained at University Health Network (UHN) between 2001 and 2002 comprising 724 spots. The TMA was constructed using up to six 0.6 mm donor cores from each RP specimen. In cases of multi focal and bilateral carcinoma, 3 donor cores were obtained from the largest foci in each lobe. Distinct tumor foci were defined as those separated by a distance of > 3mm on a single slide or > 4 mm in adjacent blocks. Different Gleason patterns were also sampled within each focus. Standard clinical follow-up data, representing 7-9 years of follow-up, were compiled for each case using a UHN RP clinical database.
Results: Heterogeneity within the PTEN locus was widespread. An association between ERG protein expression and PTEN deletions was apparent. Among prostate tumors with wild type PTEN 45% was ERG positive, while 57% of the PTEN hemizygous, and 77% of the PTEN homozygous cases were ERG positive, respectively. Correlation with clinical outcomes, such as biochemical progression, is ongoing and will be presented.
Conclusions: We conclude that ERG IHC is an emerging diagnostic modality that may help the assessment of ERG status in prostate tumors. PTEN interaction with ERG status may reveal clinical insights and allow prognostic genomic grading in prostatic carcinogenesis. Further validation studies are needed.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 227, Wednesday Morning