Comprehensive Assessment of TMPRSS2 and ETS Family Molecular Aberrations in Histologic Variants of Prostate Carcinoma
B Han, R Mehra, N Palanisamy, K Suleman, M Zhou, AM Chinnaiyan, RB Shah. University of Michigan, Ann Arbor, MI; Cleveland Clinic, Cleveland, MI
Background: Histologic variants of prostate carcinoma (PCa) account for 5 to 10% of all PCa and typically seen in association with ordinary acinar PCa. These variants often differ from latter in clinical, immunophenotypic, genetic and biologic potential. We comprehensively analyzed gene rearrangement for the ETS family member and their known 5' fusion partner TMPRSS2 in histologic variants and compared with associated acinar PCa to understand the frequency, subtype, and clonality of this common molecular event in histologic variants of PCa.
Design: A tissue microarray representing 69 cases of variant morphology (foamy gland (N=17), large duct (N=18), mucinous (N=18), small cell neuroendocrine (N=7), glomerulation (N=9)) and paired acinar morphology when present, were analyzed using break apart (TMPRSS2, ERG, ETV1, ETV4, ETV5) fluorescence in situ hybridization assays.
Results: Overall 55% of variants PCa demonstrated TMPRSS2: ETS aberrations. ERG, the most common genetic rearrangement observed in acinar PCa, was identified in 82%, 71%, 56%, 33% and 29% of mucinous, small cell, large duct, glomeruloid and foamy variant morphologies respectively (Table 1). ERG rearrangement through intronic deletion of 5'was observed exclusively (100%) in small cell and 56% of large duct PCa. Out of 54 cases that harbored paired acinar PCa, concordance of gene rearrangement between variant morphology and paired PCa was observed in 91% of cases.
Conclusions: Our result suggests that variant morphology represents a clonal expansion of primary acinar PCa. The frequency and spectrum of these genetic aberrations differ between variants. Exclusive ERG rearrangement through deletion observed in small cell PCa supports that 5' ERG rearrangement through deletion represents an aggressive molecular subtype of PCa.
Table 1. Summary of ETS rearrangment in hostologic variants of prostate carcinoma
|Histologic Variants||Rearranged||through deletion||through translocation|
|foamy gland||29% (4/14)||25% (1/4)||75% (3/4)||0% (0/13)|
|large duct||56% (9/16)||56% (5/9)||44% (4/9)||0% (0/16)|
|Glomerulation||37% (3/7)||0% (0/3)||100% (3/3)||14% (1/7)|
|Mucinous||82% (14/17)||36% (5/14)||64% (9/14)||0% (0/16)|
|small cell||71% (5/7)||100% (5/5)||0% (0/5)||0% (0/7)|
Category: Genitourinary (including renal tumors)
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 121, Monday Morning