PMID- 28845585
OWN - NLM
STAT- MEDLINE
DCOM- 20171009
LR  - 20171009
IS  - 1097-0045 (Electronic)
IS  - 0270-4137 (Linking)
VI  - 77
IP  - 14
DP  - 2017 Oct
TI  - Intrafocal heterogeneity of ERG protein expression and gene fusion pattern in 
      prostate cancer.
PG  - 1438-1445
LID - 10.1002/pros.23405 [doi]
AB  - BACKGROUND: Prostate cancer is considered to be highly heterogeneous, with 
      various morphologic features and biologic behaviors. The TMPRSS2-ERG gene fusion 
      is the most frequently observed genetic aberration in prostate cancer. The aim of 
      this study was to elucidate the intrafocal heterogeneity of ERG gene fusion 
      status. METHODS: ERG immunohistochemistry (IHC) was performed in samples from 168 
      prostate cancer patients who had undergone radical prostatectomy, and 40 cases 
      showing ERG-positive IHC staining were selected for tissue microarray (TMA) 
      construction. Two to six representative cores were selected from each tumor 
      focus. In the cases with heterogeneous ERG IHC staining intensity, the areas 
      showing different intensities were separately selected. Using the TMA blocks, IHC 
      and fluorescence in situ hybridization (FISH) were conducted to evaluate the 
      heterogeneity of ERG protein expression and ERG fusion gene patterns, 
      respectively, in a single tumor focus. Heterogeneity of ERG IHC staining was 
      defined as the simultaneous presence of negative and positive cores in the same 
      tumor focus. Heterogeneity of ERG FISH was defined by the presence of cores with 
      positive and negative FISH signals or cores with break-apart and interstitial 
      deletion FISH signals in the same tumor focus. RESULTS: A total of 202 TMA cores 
      were isolated from 40 ERG-positive cases. Of the 202 total cores, 19 were 
      negative for ERG IHC staining, and 46 showed 1+, 52 showed 2+, and 85 showed 3+ 
      ERG staining intensity. Eleven cores were negative for ERG FISH signal, 119 cores 
      showed ERG break-apart FISH signals, and the remaining 72 cores revealed 
      interstitial deletion. Intrafocal heterogeneity of ERG IHC staining was found in 
      20% (8/40) of cases, and intrafocal heterogeneity of ERG gene fusion pattern was 
      found in 32.5% (13/40) of cases. CONCLUSIONS: In summary, this study showed 
      significantly frequent intrafocal heterogeneity of ERG protein expression, gene 
      fusion status and fusion pattern. This heterogeneity can be caused by the 
      development of subclones during cancer progression or the intermingling of 
      different tumors.
CI  - (c) 2017 Wiley Periodicals, Inc.
FAU - Suh, Ja Hee
AU  - Suh JH
AD  - Department of Pathology, Seoul National University College of Medicine, Seoul, 
      Korea.
FAU - Park, Jeong Hwan
AU  - Park JH
AD  - Department of Pathology, Seoul National University College of Medicine, Seoul, 
      Korea.
AD  - Department of Pathology, SMG-SNU Boramae Medical Center, Seoul, Korea.
FAU - Lee, Cheol
AU  - Lee C
AD  - Department of Pathology, Seoul National University College of Medicine, Seoul, 
      Korea.
FAU - Moon, Kyung Chul
AU  - Moon KC
AUID- ORCID: 0000-0002-1969-8360
AD  - Department of Pathology, Seoul National University College of Medicine, Seoul, 
      Korea.
AD  - Kidney Research Institute, Medical Research Center, Seoul National University 
      College of Medicine, Seoul, Korea.
LA  - eng
PT  - Journal Article
DEP - 20170828
PL  - United States
TA  - Prostate
JT  - The Prostate
JID - 8101368
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (TMPRSS2-ERG fusion protein, human)
SB  - IM
MH  - Biomarkers, Tumor/genetics
MH  - Disease Progression
MH  - Genetic Heterogeneity
MH  - Humans
MH  - Immunohistochemistry
MH  - Male
MH  - Middle Aged
MH  - Oncogene Proteins, Fusion/*genetics
MH  - Prognosis
MH  - Prostate/*pathology
MH  - *Prostatic Neoplasms/genetics/pathology
OTO - NOTNLM
OT  - ERG
OT  - FISH
OT  - heterogeneity
OT  - immunohistochemistry
OT  - prostate cancer
EDAT- 2017/08/29 06:00
MHDA- 2017/10/11 06:00
CRDT- 2017/08/29 06:00
PHST- 2017/06/13 00:00 [received]
PHST- 2017/08/08 00:00 [accepted]
PHST- 2017/08/29 06:00 [pubmed]
PHST- 2017/10/11 06:00 [medline]
PHST- 2017/08/29 06:00 [entrez]
AID - 10.1002/pros.23405 [doi]
PST - ppublish
SO  - Prostate. 2017 Oct;77(14):1438-1445. doi: 10.1002/pros.23405. Epub 2017 Aug 28.