Comprehensive FISH Assessment Shows Association of PTEN Deletion with ERG Rearrangement during Prostate Cancer Development
B Han, R Mehra, N Palanisamy, AM Chinnaiyan, RB Shah. University of Michigan, Ann Arbor, MI
Background: Whereas ERG rearrangement and PTEN deletion are two of the most common genomic aberrations in human prostate cancer, little is known about the link between these two genomic events. Hence, we comprehensively evaluated a wide spectrum of benign tissues, premalignant and malignant lesions to characterize ERG rearrangement and PTEN deletion during prostate cancer carcinogenesis and progression.
Design: Fluorescence in situ hybridization (FISH) was employed to assess aberrations of ERG and PTEN in a cohort of 282 localized prostate cancer and 47 androgen-independent metastatic prostate cancer patients, along with 89 high grade prostatic intraepithelial neoplasia (HGPIN) foci and 73 non-neoplastic prostate tissues.
Results: ERG rearrangement was present in 47% of localized prostate cancer, 35% of metastasis and 15% of HGPIN. PTEN deletion was identified in 17% of localized cancer and 54% of metasetasis, of which homozygous deletion was observed in 6% and 24%, respectively. Only 9% of HGPINs harbored PTEN deletion, all of which were hemizygous. Further, immunohistochemistry revealed correlation of PTEN aberrations with decreased PTEN protein expression (p<0.05). Notably, PTEN deletion is significantly associated with ERG rearrangement both in localized cancer (p<0.001) and metastasis (p<0.05). Concomitance of ERG rearrangement and PTEN deletion was observed in 50% (6/12) of cases in a selective cohort of HGPINs, all of which were adjacent to cancer. Of note, ERG aberration, but not PTEN deletion, was identical both in localized cancer and adjacent HGPIN. Similarly, whereas 5% (2/41) of metastatic cancers showed discordance for PTEN deletion across multiple sites from the same patient, all metastasis (43/43, 100%) shared the same ERG status across multiple sites.
Conclusions: Our study suggests that ERG rearrangement and PTEN deletion may cooperate but contribute through different ways in prostate carcinogenesis and progression. Understanding the molecular cross-talk between these two genetic events may provide insight into understanding of prostate cancer development.
Category: Genitourinary (including renal tumors)
Monday, March 9, 2009 1:00 PM
Poster Session II # 114, Monday Afternoon