TMPRSS2-ERG fusion impacts anterior tumor location in men with prostate cancer

Kosj Yamoah, Priti Lal 2, Shivanshu Awasthi, Arash O Naghavi, Robert J Rounbehler, Travis Gerke, Anders E Berglund, Julio M Pow-Sang, Edward M Schaeffer, Jasreman Dhillon, Jong Y Park, Timothy R Rebbeck


First published: 03 November 2020


PMID: 33141952 PMCID: PMC7810127 (available on 2022-02-01) DOI: 10.1002/pros.24086


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.


© 2020 Wiley Periodicals LLC.


Full text: https://doi.org/10.1002/pros.24086


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