PMID- 30140035
OWN - NLM
STAT- MEDLINE
DCOM- 20191216
LR  - 20230210
IS  - 1530-0285 (Electronic)
IS  - 0893-3952 (Linking)
VI  - 32
IP  - 1
DP  - 2019 Jan
TI  - The combination of PTEN deletion and 16p13.3 gain in prostate cancer provides 
      additional prognostic information in patients treated with radical prostatectomy.
PG  - 128-138
LID - 10.1038/s41379-018-0107-6 [doi]
AB  - Prostate cancer is a clinically heterogeneous disease and accurately 
      risk-stratifying patients is a key clinical challenge. We hypothesized that the 
      concurrent identification of the DNA copy number alterations 10q23.3 (PTEN) 
      deletion and 16p13.3 (PDPK1) gain, related to the PI3K/AKT survival pathway, 
      would improve prognostication. We assessed PTEN deletion status using 
      fluorescence in situ hybridization (FISH) and evaluated its clinical significance 
      in combination with the 16p13.3 gain in a set of 332 primary radical 
      prostatectomy cases on a tissue microarray with clinical follow-up. The PTEN 
      deletion was detected in 34% (97/287) of the evaluable tumors and was 
      significantly associated with high Gleason grade group (P < 0.0001) and advanced 
      pathological tumor stage (pT-stage, P < 0.001). The PTEN deletion emerged as a 
      significant predictor of biochemical recurrence independent of the standard 
      clinicopathologic parameters (hazard ratio: 3.00, 95% confidence interval: 
      1.81-4.98; P < 0.0001) and further stratified patients with low and intermediate 
      risk of biochemical recurrence [Gleason grade group 1-2 (</=3 + 4), Gleason grade 
      group 2 (3 + 4), pT2, prostate-specific antigen </= 10, low and intermediate 
      CAPRA-S score; log-rank P </= 0.007]. A PTEN deletion also increased the risk of 
      distant metastasis (log-rank, P = 0.001), further supporting its role in prostate 
      cancer progression. Combining both 16p13.3 gain and PTEN deletion improved 
      biochemical recurrence risk stratification and provided prognostic information 
      beyond the established CAPRA-S score (co-alteration: hazard ratio: 4.70, 95% 
      confidence interval: 2.12-10.42; P < 0.0001). Our study demonstrates the 
      potential clinical utility of PTEN genomic deletion in low-intermediate risk 
      patients and highlights the enhanced prognostication achieved when assessed in 
      combination with another genomic biomarker related to the PI3K/AKT pathway, 
      thereby supporting their promising usefulness in clinical management of prostate 
      cancer.
FAU - Bramhecha, Yogesh M
AU  - Bramhecha YM
AD  - Division of Urology, Department of Surgery, McGill University and the Research 
      Institute of the McGill University Health Centre, Montreal, QC, Canada.
AD  - Division of Experimental Medicine, McGill University and the Research Institute 
      of the McGill University Health Centre, Montreal, QC, Canada.
FAU - Rouzbeh, Shaghayegh
AU  - Rouzbeh S
AD  - Division of Urology, Department of Surgery, McGill University and the Research 
      Institute of the McGill University Health Centre, Montreal, QC, Canada.
FAU - Guerard, Karl-Philippe
AU  - Guerard KP
AD  - Division of Urology, Department of Surgery, McGill University and the Research 
      Institute of the McGill University Health Centre, Montreal, QC, Canada.
FAU - Scarlata, Eleonora
AU  - Scarlata E
AD  - Division of Urology, Department of Surgery, McGill University and the Research 
      Institute of the McGill University Health Centre, Montreal, QC, Canada.
FAU - Brimo, Fadi
AU  - Brimo F
AD  - Department of Pathology, McGill University and the Research Institute of the 
      McGill University Health Centre, Montreal, QC, Canada.
FAU - Chevalier, Simone
AU  - Chevalier S
AD  - Division of Urology, Department of Surgery, McGill University and the Research 
      Institute of the McGill University Health Centre, Montreal, QC, Canada.
AD  - Division of Experimental Medicine, McGill University and the Research Institute 
      of the McGill University Health Centre, Montreal, QC, Canada.
FAU - Hamel, Lucie
AU  - Hamel L
AD  - Division of Urology, Department of Surgery, McGill University and the Research 
      Institute of the McGill University Health Centre, Montreal, QC, Canada.
FAU - Aprikian, Armen G
AU  - Aprikian AG
AD  - Division of Urology, Department of Surgery, McGill University and the Research 
      Institute of the McGill University Health Centre, Montreal, QC, Canada.
FAU - Lapointe, Jacques
AU  - Lapointe J
AUID- ORCID: 0000-0002-4586-8052
AD  - Division of Urology, Department of Surgery, McGill University and the Research 
      Institute of the McGill University Health Centre, Montreal, QC, Canada. 
      jacques.lapointe@mcgill.ca.
AD  - Division of Experimental Medicine, McGill University and the Research Institute 
      of the McGill University Health Centre, Montreal, QC, Canada. 
      jacques.lapointe@mcgill.ca.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20180823
PL  - United States
TA  - Mod Pathol
JT  - Modern pathology : an official journal of the United States and Canadian Academy 
      of Pathology, Inc
JID - 8806605
RN  - 0 (Biomarkers, Tumor)
RN  - EC 2.7.11.1 (3-Phosphoinositide-Dependent Protein Kinases)
RN  - EC 2.7.11.1 (PDPK1 protein, human)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (PTEN protein, human)
SB  - IM
MH  - 3-Phosphoinositide-Dependent Protein Kinases/*genetics
MH  - Adult
MH  - Aged
MH  - Biomarkers, Tumor/*genetics
MH  - DNA Copy Number Variations
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - PTEN Phosphohydrolase/*genetics
MH  - Prognosis
MH  - Prostatectomy
MH  - Prostatic Neoplasms/*genetics/mortality/*pathology
EDAT- 2018/08/25 06:00
MHDA- 2019/12/18 06:00
CRDT- 2018/08/25 06:00
PHST- 2018/03/27 00:00 [received]
PHST- 2018/06/16 00:00 [accepted]
PHST- 2018/06/16 00:00 [revised]
PHST- 2018/08/25 06:00 [pubmed]
PHST- 2019/12/18 06:00 [medline]
PHST- 2018/08/25 06:00 [entrez]
AID - S0893-3952(22)01111-5 [pii]
AID - 10.1038/s41379-018-0107-6 [doi]
PST - ppublish
SO  - Mod Pathol. 2019 Jan;32(1):128-138. doi: 10.1038/s41379-018-0107-6. Epub 2018 Aug 
      23.