Year: 2019
Type: article
Abstract: You have accessJournal of UrologyProstate Cancer: Detection & Screening I (MP13)1 Apr 2019MP13-08 RADIOGENOMIC DISSECTION OF MULTIFOCAL PROSTATE CANCER Simpa Salami*, Jeremy Kaplan, Srinivas Nallandhingal, Mandeep Takhar, Jeffrey Tosoian, Matthew Lee, Junhee Yoon, Daniel Hovelson, Komal Plouffe, Samuel Kaffenberger, Arvin George, Jeffrey Montgomery, Matthew Davenport, Sungyong You, Scott Tomlins, Nicole Curci, Hyung Kim, Daniel Spratt, Aaron Udager, and Ganesh Palapattu Simpa Salami*Simpa Salami* More articles by this author , Jeremy KaplanJeremy Kaplan More articles by this author , Srinivas NallandhingalSrinivas Nallandhingal More articles by this author , Mandeep TakharMandeep Takhar More articles by this author , Jeffrey TosoianJeffrey Tosoian More articles by this author , Matthew LeeMatthew Lee More articles by this author , Junhee YoonJunhee Yoon More articles by this author , Daniel HovelsonDaniel Hovelson More articles by this author , Komal PlouffeKomal Plouffe More articles by this author , Samuel KaffenbergerSamuel Kaffenberger More articles by this author , Arvin GeorgeArvin George More articles by this author , Jeffrey MontgomeryJeffrey Montgomery More articles by this author , Matthew DavenportMatthew Davenport More articles by this author , Sungyong YouSungyong You More articles by this author , Scott TomlinsScott Tomlins More articles by this author , Nicole CurciNicole Curci More articles by this author , Hyung KimHyung Kim More articles by this author , Daniel SprattDaniel Spratt More articles by this author , Aaron UdagerAaron Udager More articles by this author , and Ganesh PalapattuGanesh Palapattu More articles by this author View All Author Informationhttps://doi.org/10.1097/01.JU.0000555221.51086.22AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVES: Up to 20% of patients with negative multiparametric magnetic resonance imaging (MRI) harbor Gleason score ≥7 prostate cancer (PCa). In this study, we sought to elucidate the molecular basis of and determine the prognostic significance of PCa visibility on MRI. METHODS: We identified a retrospective cohort of patients who underwent MRI prior to radical prostatectomy with both MRI visible (PIRADS 3 - 5) and invisible PCa. MRI for each patient was re-reviewed and co-registered with whole-mount histopathology. DNA and RNA were co-isolated from all tumor foci pre-identified on formalin-fixed paraffin-embedded specimens. High depth, targeted DNA and RNA next generation sequencing was performed to characterize the molecular profile of each tumor focus using the Oncomine Comprehensive Panel (DNA) and a custom targeted RNAseq panel assessing PCa relevant alterations. A multigene RNAseq model was developed and validated in two independent cohorts to predict MRI visible PCa and to determine the prognostic significance of MRI visibility. RESULTS: A total of 26 primary tumor foci from 10 patients were analyzed. The median number of PCa foci was 3. Of the 14 (54%) invisible lesions on MRI, 5 (36%) were Gleason 3+4=7 and the remainder were Gleason 6. We detected high-confidence prioritized mutations in 54% (14/26) of tumor foci, 43% (6/14) of which were in MRI invisible lesions. Notable point mutations were in APC, AR, ARID1B, ATM, ATRX, BRCA2, FAT1, MAP3K1, NF1, SPEN, SPOP, TP53, and a frameshift mutation was detected in SOX2. A 9-gene RNA signature, the majority of which were under-expressed cellular organization and structure genes, was developed to predict MRI visible tumors with an AUC of 0.89. Validation of this signature in an independent data set (n = 16) yielded an AUC of 0.88 with a specificity of 100% for predicting MRI visible tumors (Figure 1). Using this RNAseq signature in a cohort of 375 patients with clinical follow up, we found that predicted MRI visibility was not an independent predictor of biochemical recurrence, metastasis-free survival, or PCa specific mortality (all p > 0.05). CONCLUSIONS: We observed under-expression of cellular organization and structural genes in MRI visible tumors compared to MRI invisible lesions. Using our validated signature to predict MRI visibility status, we found that MRI visibility is not a significant predictor of oncological outcomes. Source of Funding: Prostate Cancer Foundation Ann Arbor, MI; San Diego, CA; Ann Arbor, MI; Los Angeles, CA; Ann Arbor, MI; Los Angeles, CA; Ann Arbor, MI; Los Angeles, CA; Ann Arbor, MI© 2019 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 201Issue Supplement 4April 2019Page: e179-e180 Advertisement Copyright & Permissions© 2019 by American Urological Association Education and Research, Inc.MetricsAuthor Information Simpa Salami* More articles by this author Jeremy Kaplan More articles by this author Srinivas Nallandhingal More articles by this author Mandeep Takhar More articles by this author Jeffrey Tosoian More articles by this author Matthew Lee More articles by this author Junhee Yoon More articles by this author Daniel Hovelson More articles by this author Komal Plouffe More articles by this author Samuel Kaffenberger More articles by this author Arvin George More articles by this author Jeffrey Montgomery More articles by this author Matthew Davenport More articles by this author Sungyong You More articles by this author Scott Tomlins More articles by this author Nicole Curci More articles by this author Hyung Kim More articles by this author Daniel Spratt More articles by this author Aaron Udager More articles by this author Ganesh Palapattu More articles by this author Expand All Advertisement PDF downloadLoading ...
Source: The Journal of Urology
Authors: Simpa Salami*, Jeremy Kaplan, Srinivas Nallandhingal, Mandeep Takhar, Jeffrey Tosoian, Matthew Lee, Junhee Yoon, Daniel Hovelson, Komal Plouffe, Samuel Kaffenberger, Arvin George, Jeffrey Montgomery, Matthew Davenport, Sungyong You, Scott Tomlins, Nicole Curci, Hyung Kim, Daniel Spratt, Aaron Udager, Ganesh Palapattu
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2940867948