Prostate cancer of transition zone origin lacks TMPRSS2–ERG gene fusion

Abstract

Recent studies have shown a unique chromosomal rearrangement that leads to the fusion of 5 0 -transmembrane protein serine proteinase-2 (TMPRSS2) with the EST-related gene (ERG) in prostate cancer. In this study, we used fluorescence in situ hybridization to evaluate TMPRSS2-ERG gene fusion in prostate cancer of different zonal origins. Radical prostatectomy specimens with multifocal prostate cancer were obtained from 30 patients who were treated at our institution. Two separate tumor foci in each specimen, one in the peripheral zone and the other in the transition zone, were selected for gene fusion analysis. The selected peripheral zone tumor foci had a mean Gleason score of 6.8 (range, 6-7) and a mean tumor volume of 1.2 cm 3 (range, 0.1-4.6 cm 3 ). The selected transition zone tumor foci had a mean Gleason score of 6.7 (range, 5-8) and a mean tumor volume of 4.0 cm 3 (range, 0.5-9.0 cm 3 ). ERG gene rearrangement was not observed in any transition zone tumors; however, it was found in the peripheral zone tumors in 13 cases (43%). In 10 cases, the rearrangement was associated with the deletion of the 5 0 -end of ERG. In conclusion, we found that TMPRSS2-ERG gene fusion is associated with the zonal origin of prostate cancer. This gene fusion is prevalent in prostate cancer arising from the peripheral zone, but is lacking in prostate cancer arising from the transition zone.

ERG rearrangement is present in a subset of transition zone prostatic tumors

“…Similar to Demichelis et al 5 and in contrast to Guo et al, 24 we detected TMPRSS2-ERG gene fusion in 7 (12%) informative transition zone tumors. Of the fusion-positive transition zone prostate cancers, two were Gleason score 6 and five were Gleason score 7; two involved extraprostatic tissue, four were organ confined, and in one case the tumor involved the surgical margin of resection.…”

“…This frequency of TMPRSS2-ERG fusion is similar to the value of 30% (134 of 445) found by Attard et al, 8 but lower than the value of 49% (58 of 118) found by Perner et al 2 and 43% (13 of 30) found by Guo et al, 24 who also assessed ERG gene alterations using a FISH breakapart assay. As the incidence of ERG gene alterations have been linked to clinical stage and Gleason score, these differences may be explained, at least in part, by the distinct clinical compositions of the prostate tumor sets surveyed in each study, as suggested by Attard et al 8 Among our positive cases, deletion, rather than translocation, was found to be the main mechanism for TMPRSS2-ERG gene fusion in both transition zone prostate cancers (57%) and peripheral zone prostate cancers (58%), as previously reported in other studies.…”

“…As the incidence of ERG gene alterations have been linked to clinical stage and Gleason score, these differences may be explained, at least in part, by the distinct clinical compositions of the prostate tumor sets surveyed in each study, as suggested by Attard et al 8 Among our positive cases, deletion, rather than translocation, was found to be the main mechanism for TMPRSS2-ERG gene fusion in both transition zone prostate cancers (57%) and peripheral zone prostate cancers (58%), as previously reported in other studies. 2,24,25,33,40,41 We observed duplication of the rearranged sequence with deletion in one prostate cancer from the peripheral zone. Yoshimoto et al 3 observed duplication of TMPRSS2-ERG fusion in 6% of tumors and reported an association with worse prognosis.…”

“…The frequency of TMPRSS2-ERG fusion detected in these transition zone tumors was 15% (17/111). Recently, Guo et al 24 have found no TMPRSS2-ERG gene fusion rearrangement in any of the 30 transition zone prostate cancers examined.…”

“…16,23 Although numerous studies have been published on ERG rearrangements in prostate cancer, few focused on transition zone tumors. Recently, Guo et al 24 have examined 30 transition zone and 30 peripheral zone tumors and reported TMPRSS2-ERG gene fusion in 43% of peripheral zone and in none of the transition zone cases.…”