TMPRSS2-ERG Rearrangement in Transition Zone (TZ) Versus Anterior Peripheral Zone (PZ) Prostate Cancer: Relative Incidence and Correlation with 'TZ-LOOK' Histology
A Gopalan, C Savage, A Maschino, MA Leversha, J McGuire, HA Al-Ahmadie, SK Tickoo, WL Gerald, VE Reuter, SW Fine. MSKCC, NY, NY
Background: TMPRSS2-ERG gene rearrangement has been shown to be a common genetic event occurring in about 30-70% of prostate cancer (PC). Zonal differences in the incidence have not been well studied with the only published study to date showing that rearrangement was completely lacking in transition zone PC. We have previously studied a large cohort of whole-mounted, entirely submitted radical prostatectomy specimens which contained dominant anterior tumors. These were defined using strict anatomic considerations, including relationships between glandular zones and the anterior fibromuscular stroma and the variability of anterior prostatic anatomy from apex through base. It has recently been shown that the 'clear cell' histology attributed to TZ tumors by McNeal (TZ-LOOK) may be seen in cancers arising from either TZ or PZ, although it is more frequent in TZ-PC. We studied a well-characterized cohort of anterior PZ and TZ cancers for TMPRSS2-ERG rearrangement status and correlated it with TZ-LOOK histology.
Design: We analyzed TMPRSS2-ERG gene rearrangement status using FISH in 61 TZ and 75 anterior PZ cancers, arrayed on two tissue microarrays as triplicate cores. FISH break-apart probe used BAC clones against 3' ERG and 3' and 5' TMPRSS2. H&E sections were used to assess the presence of the TZ-LOOK in these samples.
Results: FISH results were available for 58 TZ and 71 anterior PZ samples. The overall incidence of rearrangement (17%) was lower than that previously reported in radical prostatectomy-based series. Significantly, fewer TZ cancers were found to have a rearrangement (4/58; 6.9%) than anterior PZ cancers (18/71; 25%) [p=0.001]. Deletion was the sole mechanism of rearrangement in all TZ cancers. TZ-LOOK histology was present in 10/75 (13%) anterior PZ tumors and 22/61 (36%) TZ tumors. Five percent of PC with and 17% without TZ-LOOK histology had rearrangement, regardless of zone of origin.
Conclusions: TMPRSS2-ERG rearrangement occurs in prostate cancers arising from both transition zone and peripheral zone, with all transition zone cancers rearranged through deletion. The incidence of rearrangement is significantly lower in transition zone tumors. Although infrequent, TMPRSS2-ERG rearrangement may be present in tumors displaying TZ-LOOK histology irrespective of zonal origin.
Category: Genitourinary (including renal tumors)
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 130, Wednesday Afternoon