Deletion of 8p is an independent prognostic parameter in prostate cancer

Abstract

Deletion of chromosome 8p is the second most frequent genomic alteration in prostate cancer. To better understand its clinical significance, 8p deletion was analyzed by fluorescence in-situ hybridization on a prostate cancer tissue microarray. 8p deletion was found in 2,581 of 7,017 cancers (36.8%), and was linked to unfavorable tumor phenotype. 8p deletion increased from 29.5% in 4,456 pT2 and 47.8% in 1,598 pT3a to 53.0% in 931 pT3b-pT4 cancers (P < 0,0001). Deletions of 8p were detected in 25.5% of 1,653 Gleason ≤ 3 + 3, 36.6% of 3,880 Gleason 3 + 4, 50.2% of 1,090 Gleason 4 + 3, and 51.1% of 354 Gleason ≥ 4 + 4 tumors (P < 0,0001). 8p deletions were strongly linked to biochemical recurrence (P < 0.0001) independently from established pre- and postoperative prognostic factors (P = 0.0100). However, analysis of morphologically defined subgroups revealed, that 8p deletion lacked prognostic significance in subgroups with very good (Gleason ≤ 3 + 3, 3 + 4 with ≤ 5% Gleason 4) or very poor prognosis (pT3b, Gleason ≥ 8, pN1). 8p deletions were markedly more frequent in cancers with (53.5%) than without PTEN deletions (36.4%; P < 0,0001) and were slightly more frequent in ERG-positive (40.9%) than in ERG-negative cancers (34.7%, P < 0.0001) due to the association with the ERG-associated PTEN deletion. Cancers with 8p/PTEN co-deletions had a strikingly worse prognosis than cancers with deletion of PTEN or 8p alone (P ≤ 0.0003). In summary, 8p deletion is an independent prognostic parameter in prostate cancer that may act synergistically with PTEN deletions. Even statistically independent prognostic biomarkers like 8p may have limited clinical impact in morphologically well defined high or low risk cancers.

13q deletion is linked to an adverse phenotype and poor prognosis in prostate cancer

“…Even though our multivariate modeling suggested that 13q deletion testing may hold promise for a clinical test in preoperative situations, the prognostic significance of 13q deletion was rather limited and the risk of recurrence within 5 years differed only 10% between cancers with and without 13q deletion. This is less than previously observed for other deletions such as 10q (25% difference in the risk for PSA recurrence between PTEN deleted and undeleted cancers), 8p (20%) 6q (15%), 5q (15%), and 17p (10%) . However, it is possible that a combined analysis of several deletion loci (i.e., in order to determine a cancers deletion load) will lead to a better prediction of prognosis than analysis of single deletion loci.…”

“…Our findings identify 13q deletion as a genomic alteration that is largely unrelated to ERG‐status. Using the same set of cancers we have previously identified a few other deletions, including loss of 12p and 8p that are unrelated to the ERG status.…”

“…Furthermore, these scoring criteria had been successfully used to analyze other deletions in our prognosis TMA . In comparison with these studies 13q deletion is the third most frequent genomic alteration after TMPRSS2:ERG fusion (52%) and deletion of 8p (36%) being equally frequent as deletions of 16q23 (21%) …”

“…This result is typical for deletions in prostate cancer. Using our large TMA resource we have studied deletions of PTEN , 3p, 5q, 6q, 16q, 8p, 18q, and 12p and found that all of these deletions are linked to an adverse tumor phenotype. Although the role of PTEN and CHD1 for 10q and 5q deletions is well established in prostate cancer, we strongly believe that most of these deletions might harbor more than 1 tumor relevant gene.…”

“…Depending on the chromosomal area deletions occur in up to 40% of prostate cancers . All chromosomal deletions that were analyzed in large cohorts of prostate cancers were found to be associated with advanced disease and early recurrence . Interestingly, most chromosomal deletions are strongly linked to either ERG‐negative or ERG‐positive cancers .…”