PMID- 30900303 OWN - NLM STAT- MEDLINE DCOM- 20200114 LR - 20200114 IS - 1097-0045 (Electronic) IS - 0270-4137 (Linking) VI - 79 IP - 8 DP - 2019 Jun TI - The expression profile and heterogeneity analysis of ERG in 633 consecutive prostate cancers from a single center. PG - 819-825 LID - 10.1002/pros.23785 [doi] AB - BACKGROUND: Overexpression of ERG protein resulting from TMPRSS2:ERG rearrangement is highly specific for prostate cancer (PCa). However, the biological function of this fusion protein and its relationship with clinicopathological features still remain controversial. METHOD: In this study, we evaluated ERG protein expression/gene rearrangement and heterogeneity by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in a cohort of 633 consecutive PCa initially diagnosed by core-needle biopsy in the West China Hospital. RESULT: Overall, ERG protein expression was detected in 16.7% (106 of 633) cases, and frequently observed in PCa patients less than 60 years of age (31.9% vs 15.5%, P = 0.004) and in PCa with Gleason score less than 8 (20.0% vs 13.4%, P = 0.027), but infrequently observed in cases with intraductal carcinoma of the prostate (IDC-P) (10.0% vs 18.6%, P = 0.012). Follow-up analysis found that patients who progressed to castration-resistant prostate cancer (CRPC) have a lower frequency of ERG protein expression at initial biopsies compared to androgen deprivation therapy (ADT)-sensitive cases (14.1% vs 23.5%, P = 0.042), but Kaplan-Meier curve showed that ERG protein expression was not an independent prognostic marker. Of all the 106 ERG-positive cases, eight cases (7.5%) exhibited heterogeneous expression of ERG protein, in which ERG was only positive in tumors with Gleason pattern 3, but negative in Gleason pattern 4. The FISH analysis was consistent with IHC in six of these cases. In the other two cases, ERG rearrangement was detected in tumors with both Gleason pattern 3 and 4 by FISH, despite the negative protein expression in Gleason pattern 4. In case 1, a repeated biopsy was performed when the disease progressed to CRPC, and no ERG-positive cells were identified neither by IHC nor FISH. CONCLUSION: This was by far the largest series of ERG expression and heterogeneity analysis in Chinese PCa. The ERG rearrangement seemed to be frequently expressed in patients with relatively younger age and lower Gleason score and infrequently expressed in PCa with the IDC-P. PCa with positive ERG were less frequently to progress to CRPC, but there was no prognostic significance of ERG expression. In heterogeneous cases, ERG protein was detectable only in tumors with Gleason pattern 3 but not in pattern 4. Tumor cells with positive ERG expression/rearrangement seemed easily response to ADT. CI - (c) 2019 Wiley Periodicals, Inc. FAU - Nie, Ling AU - Nie L AD - State Key Laboratory of Biotherapy, Department of Pathology, West China Hospital, West China Medical School, Sichuan University, Chengdu, China. FAU - Pan, Xiuyi AU - Pan X AD - State Key Laboratory of Biotherapy, Department of Pathology, West China Hospital, West China Medical School, Sichuan University, Chengdu, China. FAU - Zhang, Mengni AU - Zhang M AD - State Key Laboratory of Biotherapy, Department of Pathology, West China Hospital, West China Medical School, Sichuan University, Chengdu, China. FAU - Yin, Xiaoxue AU - Yin X AD - State Key Laboratory of Biotherapy, Department of Pathology, West China Hospital, West China Medical School, Sichuan University, Chengdu, China. FAU - Gong, Jing AU - Gong J AD - State Key Laboratory of Biotherapy, Department of Pathology, West China Hospital, West China Medical School, Sichuan University, Chengdu, China. FAU - Chen, Xueqin AU - Chen X AD - State Key Laboratory of Biotherapy, Department of Pathology, West China Hospital, West China Medical School, Sichuan University, Chengdu, China. FAU - Xu, Miao AU - Xu M AD - State Key Laboratory of Biotherapy, Department of Pathology, West China Hospital, West China Medical School, Sichuan University, Chengdu, China. FAU - Zhou, Qiao AU - Zhou Q AD - State Key Laboratory of Biotherapy, Department of Pathology, West China Hospital, West China Medical School, Sichuan University, Chengdu, China. FAU - Chen, Ni AU - Chen N AUID- ORCID: 0000-0002-0628-0723 AD - State Key Laboratory of Biotherapy, Department of Pathology, West China Hospital, West China Medical School, Sichuan University, Chengdu, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190322 PL - United States TA - Prostate JT - The Prostate JID - 8101368 RN - 0 (ERG protein, human) RN - 0 (Transcriptional Regulator ERG) RN - EC 3.4.21.- (Serine Endopeptidases) RN - EC 3.4.21.- (TMPRSS2 protein, human) SB - IM MH - Biopsy, Large-Core Needle/methods MH - Carcinoma, Intraductal, Noninfiltrating/genetics/*metabolism/pathology MH - Cohort Studies MH - Gene Expression MH - Gene Rearrangement MH - Genetic Heterogeneity MH - Humans MH - Image-Guided Biopsy/methods MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Male MH - Middle Aged MH - Neoplasm Grading MH - Prognosis MH - Prostatic Neoplasms/genetics/*metabolism/pathology MH - Prostatic Neoplasms, Castration-Resistant/genetics/*metabolism/pathology MH - Serine Endopeptidases/genetics/metabolism MH - Transcriptional Regulator ERG/biosynthesis/genetics MH - Tumor Burden OTO - NOTNLM OT - ERG OT - heterogeneity OT - prostate cancer OT - rearrangement EDAT- 2019/03/23 06:00 MHDA- 2020/01/15 06:00 CRDT- 2019/03/23 06:00 PHST- 2018/11/10 00:00 [received] PHST- 2019/01/20 00:00 [revised] PHST- 2019/02/14 00:00 [accepted] PHST- 2019/03/23 06:00 [pubmed] PHST- 2020/01/15 06:00 [medline] PHST- 2019/03/23 06:00 [entrez] AID - 10.1002/pros.23785 [doi] PST - ppublish SO - Prostate. 2019 Jun;79(8):819-825. doi: 10.1002/pros.23785. Epub 2019 Mar 22.