PMID- 26178158 OWN - NLM STAT- MEDLINE DCOM- 20160426 LR - 20181113 IS - 1097-0045 (Electronic) IS - 0270-4137 (Print) IS - 0270-4137 (Linking) VI - 75 IP - 14 DP - 2015 Oct TI - PTEN loss and ERG protein expression are infrequent in prostatic ductal adenocarcinomas and concurrent acinar carcinomas. PG - 1610-9 LID - 10.1002/pros.23042 [doi] AB - BACKGROUND: Prostatic ductal adenocarcinoma is an unusual and aggressive morphologic subtype of prostate cancer. PTEN gene deletion and ERG gene rearrangement are among the most common genomic changes in acinar prostate cancers. Though ductal adenocarcinoma most commonly occurs with synchronous usual-type acinar adenocarcinoma, little is known about the molecular phenotype of these mixed tumors. METHODS: We used genetically validated immunohistochemistry (IHC) assays to assess PTEN and ERG status in a group of 37 surgically treated ductal adenocarcinomas and 18 synchronous acinar adenocarcinomas where we have previously reported ERG gene rearrangement status by fluorescence in situ hybridization (FISH). A group of 34 stage and grade-matched pure acinar adenocarcinoma cases was studied as a control. RESULTS: ERG IHC was highly concordant with ERG FISH results, with 100% (36/36) concordance among ductal adenocarcinomas and 91% (31/34) concordance among 34 pure acinar carcinomas. Similar to previous FISH results, ERG expression by IHC was significantly less common among ductal adenocarcinomas (11% or 4/37) and their synchronous acinar tumors (6% or 1/18) compared to matched pure acinar adenocarcinoma cases (50% or 17/34; P = 0.0005 and 0.002, respectively). PTEN loss by IHC was also less common among ductal adenocarcinomas (18% or 6/34) and their synchronous acinar tumors (22% or 4/18) compared to matched pure acinar carcinomas (50% or 17/34; P = 0.01 and 0.08, respectively). As expected, PTEN loss was enriched among ERG positive compared to ERG-negative tumors in the pure acinar tumor control group (2.5-fold enrichment; P = 0.04) however this was not observed among the ductal adenocarcinomas (1.5 fold enrichment; P = NS). Of ductal adenocarcinomas with an evaluable synchronous acinar component, ERG status was concordant in 94% (17/18) and PTEN status was concordant in 94% (16/17). CONCLUSIONS: Based on PTEN and ERG, ductal adenocarcinomas and their concurrent acinar carcinomas may be clonally related in some cases and show important molecular differences from pure acinar carcinoma. CI - (c) 2015 Wiley Periodicals, Inc. FAU - Morais, Carlos L AU - Morais CL AD - Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD. FAU - Herawi, Mehsati AU - Herawi M AD - Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD. FAU - Toubaji, Antoun AU - Toubaji A AD - Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD. FAU - Albadine, Roula AU - Albadine R AD - Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD. FAU - Hicks, Jessica AU - Hicks J AD - Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD. FAU - Netto, George J AU - Netto GJ AD - Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD. AD - Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD. AD - Department of Urology, Johns Hopkins Medical Institutions, Baltimore, MD. FAU - De Marzo, Angelo M AU - De Marzo AM AD - Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD. AD - Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD. AD - Department of Urology, Johns Hopkins Medical Institutions, Baltimore, MD. FAU - Epstein, Jonathan I AU - Epstein JI AD - Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD. AD - Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD. AD - Department of Urology, Johns Hopkins Medical Institutions, Baltimore, MD. FAU - Lotan, Tamara L AU - Lotan TL AD - Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD. AD - Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD. LA - eng GR - P30 CA006973/CA/NCI NIH HHS/United States GR - P50 CA058236/CA/NCI NIH HHS/United States GR - P50CA58236/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20150714 PL - United States TA - Prostate JT - The Prostate JID - 8101368 RN - 0 (Biomarkers, Tumor) RN - 0 (ERG protein, human) RN - 0 (Trans-Activators) RN - 0 (Transcriptional Regulator ERG) RN - EC 3.1.3.67 (PTEN Phosphohydrolase) RN - EC 3.1.3.67 (PTEN protein, human) SB - IM MH - Biomarkers, Tumor/*biosynthesis MH - Carcinoma, Acinar Cell/*metabolism/pathology MH - Carcinoma, Ductal/*metabolism/pathology MH - Gene Expression Regulation, Neoplastic MH - Humans MH - Male MH - PTEN Phosphohydrolase/*deficiency MH - Prostatic Neoplasms/*metabolism/pathology MH - Trans-Activators/*biosynthesis MH - Transcriptional Regulator ERG PMC - PMC4537350 MID - NIHMS708292 OTO - NOTNLM OT - ERG OT - PTEN OT - ductal adenocarcinoma OT - endometrioid OT - immunohistochemistry OT - prostatic adenocarcinoma COIS- Disclosure/Conflicts of Interest: The authors have no disclosures/conflicts of interest to declare. EDAT- 2015/07/17 06:00 MHDA- 2016/04/27 06:00 PMCR- 2016/10/01 CRDT- 2015/07/17 06:00 PHST- 2015/05/05 00:00 [received] PHST- 2015/05/27 00:00 [accepted] PHST- 2015/07/17 06:00 [entrez] PHST- 2015/07/17 06:00 [pubmed] PHST- 2016/04/27 06:00 [medline] PHST- 2016/10/01 00:00 [pmc-release] AID - 10.1002/pros.23042 [doi] PST - ppublish SO - Prostate. 2015 Oct;75(14):1610-9. doi: 10.1002/pros.23042. Epub 2015 Jul 14.