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

Abstract

Deletions of chromosome arm 13q belong to the most frequent molecular alterations in prostate cancer. To better understand the role of 13q deletion in prostate cancer we took advantage of our large prostate cancer tissue microarray comprising more than 12 000 cancer samples with full pathological and clinical follow-up data. Fluorescence in situ hybridization with probes for ENOX1 (13q14.11) and the retinoblastoma gene (RB1, 13q14.2) was employed. A 13q deletion was found in 21% of 7375 analyzable cancers. Deletions were always heterozygous and associated with high Gleason grade (P < .0001), advanced tumor stage (P < .0001), high preoperative prostate-specific antigen (PSA) levels (P = .0125), lymph node metastasis (P = .0377), positive resection margin (P = .0064), and early biochemical recurrence (P < .0001). 13q deletions were marginally more frequent in prostate cancers with negative ERG status (22.9%) than in ERG-positive tumors (18.7%; P < .0001). Loss of 13q predicted patient prognosis independently from established prognostic parameters that are available at the time of biopsy (P = .0004), including preoperative PSA level, clinical tumor stage, and biopsy Gleason grade. In summary, the results of our study identify 13q deletion as a frequent event in prostate cancer, which is linked to an adverse phenotype and poor prognosis in this disease.

Reduced KLK2 expression is a strong and independent predictor of poor prognosis in ERG‐negative prostate cancer

“…[18][19][20][21][22][23][24][25][26][27]37,38 Remarkably, most deletions are related to the TMPRSS2:ERG status. [18][19][20][21][22][23][24][25][26][27] For example, deletions of 6q and 5q predominate in ERG-negative cancers, 19,20,39 whereas deletions of PTEN, TP53, and 3p13 are linked to ERG-positive cancers. 18,22,26,38 .0171…”

Secreted Frizzled-Related Protein 4 (SFRP4) Is an Independent Prognostic Marker in Prostate Cancers Lacking TMPRSS2: ERG Fusions

“…For internal controls, each TMA block also contained various control tissues, including normal prostate tissue. The attached molecular database included data on Ki67 labeling Index (Ki67LI) from 5492 tumors, expanded from [ 29 ], ERG protein expression from 8134 and ERG rearrangement analysis by fluorescence in situ hybridization (FISH) from 5515 tumors [ 30 , 31 ], as well as deletion status of 3p13 (FOXP1) from 5503 tumors [ 32 ], 5q21 (CHD1) f rom 6145 tumors [ 33 ], 6q15 (MAP3K7) from 4663 tumors [ 34 ], 8p21 from 5556 tumors [ 35 ], 10q23 (PTEN) from 5158 tumors [ 36 ], 12p13 (CDKN1B) from 4887 tumors [ 37 ], 12q24 from 5721 tumors [ 38 ], 13q14 (FOXO1, RB1) from 5915 tumors [ 39 ], 16q24 from 4413 tumors [ 40 ], 17p13 (TP53) from 6437 tumors [ 41 ] and 18q21 from 5578 tumors [ 42 ].…”

Upregulation of the transcription factor TFAP2D is associated with aggressive tumor phenotype in prostate cancer lacking the TMPRSS2:ERG fusion

“…Most chromosomal deletions occurring in prostate cancer are linked to either positive (PTEN,3p,8p,16q,17p) (Krohn et al 2013;Kluth et al 2017;Krohn et al 2012;Kluth et al 2015b;Kluth et al 2014) or negative (6q, 5q, 13q, 18q) (Burkhardt et al 2013;Kluth et al 2013;Kluth et al 2018;Kluth et al 2016) ERG status. The evaluation whether a relationship exists between deletions and the expression of proteins that are also ERG related must therefore be done in subgroups of ERG positive and ERG negative cancers.…”

“…For internal controls, each TMA block also contained various control tissues, including normal prostate tissue. The molecular database attached to the TMA contained previously compiled data on ERG expression in 10,678 (Weischenfeldt et al 2013), ERG break-apart FISH analysis in 7099 (expanded from (Minner et al 2011), Ki67-labeling index in 4426 (expanded from (Minner et al 2010), androgen receptor (AR) expression in 7856 cancers (Weischenfeldt et al 2013) and deletion status of 3p14 (FOXP1) in 7201 cases (expanded from (Krohn et al 2013), 5q21 (CHD1) in 8074 (expanded from (Burkhardt et al 2013), 6q15 (MAP 3 K7) in 6069 cases (expanded from (Kluth et al 2013), 8p21 in 7001 cases (expanded from (Kluth et al 2017), PTEN (10q23) in 6803 cases (expanded from (Krohn et al 2012), 12p13 (CDKN1B) in 6187 cases (expanded from (Kluth et al 2015a), 12q24 in 7435 cases (expanded from (Weischenfeldt et al 2013), 13q14 in 7499 cases (expanded from (Kluth et al 2018), 16q24 in 5493 cases (expanded from (Kluth et al 2015b), 17p13 (TP53) in 8307 cases (expanded from (Kluth et al 2014), and 18q21 in 7032 cases (expanded from (Kluth et al 2016). The usage of archived diagnostic left-over tissues for manufacturing of tissue microarrays, their analysis for research purposes and patient data analysis has been approved by local laws (HmbKHG, §12,1) and by the local ethics committee (Ethics commission Hamburg, WF-049/09).…”