@article{6abdd5631356447285a88aac6a56160b,
title = "TMPRSS2-ERG fusion impacts anterior tumor location in men with prostate cancer",
abstract = "Background: In prostate cancer (PCa), lack of androgen receptor (AR) regulated TMPRSS2-ETS-related gene (ERG) gene fusion (ERGnegative) status has been associated with African American race; however, the implications of ERG status for the location of dominant tumors within the prostate remains understudied. Methods: An African American-enriched multiinstitutional cohort of 726 PCa patients consisting of both African American men (AAM; n = 254) and European American men (EAM; n = 472) was used in the analyses. Methods of categorical analysis were used. Messenger RNA (mRNA) expression differences between anterior and posterior tumor lesions were analyzed using Wilcoxon rank-sum tests with multiple comparison corrections. Results: Anti-ERG immunohistochemistry staining showed that the association between ERG status and anterior tumors is independent of race and is consistently robust for both AAM (ERGnegative 81.4% vs. ERGpositive 18.6%; p =.005) and EAM (ERGnegative 60.4% vs. ERGpositive 39.6%; p <.001). In a multivariable model, anterior tumors were more likely to be IHC-ERGnegative (odds ratio [OR]: 3.20; 95% confidence interval [CI]: 2.14–4.78; p <.001). IHC-ERGnegative were also more likely to have high-grade tumors (OR: 1.73; 95% CI: 1.06–2.82; p =.02). In the exploratory genomic analysis, mRNA expression of location-dependent genes is highly influenced by ERG status and African American race. However, tumor location did not impact the expression of AR or the major canonical AR-target genes (KLK3, AMACR, and MYC). Conclusions: ERGnegative tumor status is the strongest predictor of anterior prostate tumors, regardless of race. Furthermore, AR expression and canonical AR signaling do not impact tumor location.",
keywords = "AR signaling, African American, TMPRSS2-ERG, prostate cancer, tumor location",
author = "Kosj Yamoah and Priti Lal and Shivanshu Awasthi and Naghavi, {Arash O.} and Rounbehler, {Robert J.} and Travis Gerke and Berglund, {Anders E.} and Pow-Sang, {Julio M.} and Schaeffer, {Edward M.} and Jasreman Dhillon and Park, {Jong Y.} and Rebbeck, {Timothy R.}",
note = "Funding Information: The authors would like to thank Alex Lopez, MD, Shelly Mahajan, MD, and Sahar Jalali‐Farahani, MD for their support in the completion of pathologic review of the study cases. Editorial assistance was provided by the Moffitt Cancer Center's Scientific Editing Department by Dr Paul Fletcher & Daley Drucker. No compensation was given beyond their regular salaries. This work has been supported in part by the Tissue Core at the H. Lee Moffitt Cancer Center & Research Institute, a comprehensive cancer center designated by the National Cancer Institute and funded in part by Moffitt's Cancer Center Support Grant (P30‐CA076292). This research was supported by the American Cancer Society MRSG‐17‐108‐01‐TBG (to KY), the V Foundation (to KY and JYP) and PHS grant R01‐CA084734 (to TRR), P60‐MD006900 (to TRR), and P20‐CA233255 (to KY and TRR). This work is also supported in part by the Molecular Genomics Core Facilities at the Moffitt Cancer Center through its NCI CCSG grant (P30‐CA76292). Funding Information: The authors would like to thank Alex Lopez, MD, Shelly Mahajan, MD, and Sahar Jalali-Farahani, MD for their support in the completion of pathologic review of the study cases. Editorial assistance was provided by the Moffitt Cancer Center's Scientific Editing Department by Dr Paul Fletcher & Daley Drucker. No compensation was given beyond their regular salaries. This work has been supported in part by the Tissue Core at the H. Lee Moffitt Cancer Center & Research Institute, a comprehensive cancer center designated by the National Cancer Institute and funded in part by Moffitt's Cancer Center Support Grant (P30-CA076292). This research was supported by the American Cancer Society MRSG-17-108-01-TBG (to KY), the V Foundation (to KY and JYP) and PHS grant R01-CA084734 (to TRR), P60-MD006900 (to TRR), and P20-CA233255 (to KY and TRR). This work is also supported in part by the Molecular Genomics Core Facilities at the Moffitt Cancer Center through its NCI CCSG grant (P30-CA76292). Publisher Copyright: {\textcopyright} 2020 Wiley Periodicals LLC",
year = "2021",
month = feb,
day = "1",
doi = "10.1002/pros.24086",
language = "English (US)",
volume = "81",
pages = "109--117",
journal = "Prostate",
issn = "0270-4137",
publisher = "Wiley-Liss Inc.",
number = "2",
}
