Abstract
Background:
Multiparametric magnetic resonance imaging (mpMRI) has been increasingly used for prostate cancer (PCa). Recent studies identified distinct molecular subclasses of PCa with recurrent genomic alterations. However, the associations between molecular alterations in PCa and characteristics on mpMRI are unknown. Therefore, the objective of this study was to investigate recurrent molecular alterations in PCa and their associations with mpMRI features.
Methods:
Sixty-two PCa nodules >0.5 cm had a preoperative mpMRI. Nodules were evaluated for ERG rearrangement, PTEN deletion, SPINK1 overexpression, SPOP mutation and CHD1 deletion. Each PCa focus was matched to the corresponding location on mpMRI. Lesions were scored by single observer according to the PI-RADSv2 scale.
Results:
Of the 62 nodules, 22 (35.5%) were ERG positive, 6 (9.7%) had SPINK1 overexpression, 6 (9.7%) had SPOP mutations, 4 (6.5%) had CHD1 deletions and 1 (1.6%) had PTEN deletion. All of the nodules with CHD1 deletions were not visible on mpMRI (P=0.037). All of the nodules with SPINK1 overexpression were visible on mpMRI, although the association was not statistically significant (P=0.06). There were no significant associations between any molecular alteration with the severity of the PI-RADS scores (all P>0.05).
Conclusions:
This investigation represents the first description of an association between recurrent molecular alterations and the characterization of PCa nodules on mpMRI. This study can be considered hypothesis-generating for future studies to rigorously evaluate the association of specific PCa molecular subclasses with imaging features and potentially define specific subsets of PCa for which the utility of MRI is higher or lower.
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References
Shariat S, Kattan M, Vickers A, Karakiewicz P, Scardino P . Critical review of prostate cancer predictive tools. Future Oncol 2009; 5: 1555–1584.
Lu-Yao GL, Albertsen PC, Moore DF, Shih W, Lin Y, DiPaola RS et al. Outcomes of localized prostate cancer following conservative management. JAMA 2009; 302: 1202–1209.
Resnick MJ, Penson DF . Functional outcomes after treatment for prostate cancer. N Engl J Med 2013; 368: 1654.
Kaffenberger SD, Barbieri CE . Molecular subtyping of prostate cancer. Curr Opin Urol 2016; 26: 213–218.
Cancer Genome Atlas Research Network. The molecular taxonomy of primary prostate cancer. Cell 2015; 163: 1011–1025.
Grasso CS, Wu YM, Robinson DR, Cao X, Dhanasekaran SM, Khan AP et al. The mutational landscape of lethal castration-resistant prostate cancer. Nature 2012; 487: 239–243.
Barbieri CE, Baca SC, Lawrence MS, Demichelis F, Blattner M, Theurillat JP et al. Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer. Nat Genet 2012; 44: 685–689.
Tomlins SA, Rhodes DR, Perner S, Dhanasekaran SM, Mehra R, Sun XW et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science 2005; 310: 644–648.
Soller MJ, Isaksson M, Elfving P, Soller W, Lundgren R, Panagopoulos I . Confirmation of the high frequency of the TMPRSS2/ERG fusion gene in prostate cancer. Genes Chromosomes Cancer 2006; 45: 717–719.
Yoshimoto M, Joshua AM, Chilton-Macneill S, Bayani J, Selvarajah S, Evans AJ et al. Three-color FISH analysis of TMPRSS2/ERG fusions in prostate cancer indicates that genomic microdeletion of chromosome 21 is associated with rearrangement. Neoplasia 2006; 8: 465–469.
Lapointe J, Kim YH, Miller MA, Li C, Kaygusuz G, van de Rijn M et al. A variant TMPRSS2 isoform and ERG fusion product in prostate cancer with implications for molecular diagnosis. Mod Pathol 2007; 20: 467–473.
Mehra R, Tomlins SA, Shen R, Nadeem O, Wang L, Wei JT et al. Comprehensive assessment of TMPRSS2 and ETS family gene aberrations in clinically localized prostate cancer. Mod Pathol 2007; 20: 538–544.
Perner S, Mosquera JM, Demichelis F, Hofer MD, Paris PL, Simko J et al. TMPRSS2-ERG fusion prostate cancer: an early molecular event associated with invasion. Am J Surg Pathol 2007; 31: 882–888.
Demichelis F, Setlur SR, Beroukhim R, Perner S, Korbel JO, Lafargue CJ et al. Distinct genomic aberrations associated with ERG rearranged prostate cancer. Genes Chromosomes Cancer 2009; 48: 366–380.
Berg KD, Vainer B, Thomsen FB, Roder MA, Gerds TA, Toft BG et al. ERG protein expression in diagnostic specimens is associated with increased risk of progression during active surveillance for prostate cancer. Eur Urol 2014; 66: 851–860.
Lindberg J, Klevebring D, Liu W, Neiman M, Xu J, Wiklund P et al. Exome sequencing of prostate cancer supports the hypothesis of independent tumour origins. Eur Urol 2013; 63: 347–353.
Turkbey B, Mani H, Shah V, Rastinehad AR, Bernardo M, Pohida T et al. Multiparametric 3 T prostate magnetic resonance imaging to detect cancer: histopathological correlation using prostatectomy specimens processed in customized magnetic resonance imaging based molds. J Urol 2011; 186: 1818–1824.
Siddiqui MM, Rais-Bahrami S, Turkbey B, George AK, Rothwax J, Shakir N et al. Comparison of MR/ultrasound fusion-guided biopsy with ultrasound-guided biopsy for the diagnosis of prostate cancer. JAMA 2015; 313: 390–397.
Prensner JR, Chinnaiyan AM, Srivastava S . Systematic, evidence-based discovery of biomarkers at the NCI. Clin Exp Metastasis 2012; 29: 645–652.
Srivastava S, Rossi SC . Early detection research program at the NCI. Int J Cancer 1996; 69: 35–37.
American College of Radiology. MR prostate imaging reporting and data system version 2.0. Available at http://www.acr.org/Quality-Safety/Resources/PIRADS/. Accessed April 2017..
Park K, Tomlins SA, Mudaliar KM, Chiu YL, Esgueva R, Mehra R et al. Antibody-based detection of ERG rearrangement-positive prostate cancer. Neoplasia 2010; 12: 590–598.
Berger MF, Lawrence MS, Demichelis F, Drier Y, Cibulskis K, Sivachenko AY et al. The genomic complexity of primary human prostate cancer. Nature 2011; 470: 214–220.
Terry S, Nicolaiew N, Basset V, Semprez F, Soyeux P, Maille P et al. Clinical value of ERG, TFF3, and SPINK1 for molecular subtyping of prostate cancer. Cancer 2015; 121: 1422–1430.
Yoshimoto M, Joshua AM, Cunha IW, Coudry RA, Fonseca FP, Ludkovski O et al. Absence of TMPRSS2:ERG fusions and PTEN losses in prostate cancer is associated with a favorable outcome. Mod Pathol 2008; 21: 1451–1460.
Renard-Penna R, Cancel-Tassin G, Comperat E, Varinot J, Léon P, Roupret M et al. Multiparametric magnetic resonance imaging predicts postoperative pathology but misses aggressive prostate cancers as assessed by cell cycle progression score. J Urol 2015; 194: 1617–1623.
Stoyanova R, Pollack A, Takhar M, Lynne C, Parra N, Lam LL et al. Association of multiparametric MRI quantitative imaging features with prostate cancer gene expression in MRI-targeted prostate biopsies. Oncotarget 2016; 7: 53362–53376.
Tomlins SA, Rhodes DR, Yu J, Varambally S, Mehra R, Perner S et al. The role of SPINK1 in ETS rearrangement-negative prostate cancers. Cancer Cell 2008; 13: 519–528.
Ateeq B, Tomlins SA, Laxman B, Asangani IA, Cao Q, Cao X et al. Therapeutic targeting of SPINK1-positive prostate cancer. Sci Transl Med 2011; 3: 72ra17.
Porten SP, Smith A, Odisho AY, Litwin MS, Saigal CS, Carroll PR et al. Updated trends in imaging use in men diagnosed with prostate cancer. Prostate Cancer Prostatic Dis 2014; 17: 246–251.
Esgueva R, Park K, Kim R, Kitabayashi N, Barbieri CE, Dorsey PJ et al. Next-generation prostate cancer biobanking: toward a processing protocol amenable for the International Cancer Genome Consortium. Diagn Mol Pathol 2012; 21: 61–68.
Acknowledgements
This study was funded by EDRN NCI U01 CA111275-09 (MAR and JMM), NCI R01 CA125612-05A1 and K08CA187417-02), the Prostate Cancer Foundation, and the Urology Care Foundation (Rising Star in Urology Research Award to CEB). CEB is a Damon Runyon Clinical Investigator supported (in part) by the Damon Runyon Cancer Research Foundation. This work was also supported in part by the Translational Research Program at WCM Pathology and Laboratory Medicine.
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Lee, D., Fontugne, J., Gumpeni, N. et al. Molecular alterations in prostate cancer and association with MRI features. Prostate Cancer Prostatic Dis 20, 430–435 (2017). https://doi.org/10.1038/pcan.2017.33
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DOI: https://doi.org/10.1038/pcan.2017.33
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