title: Clonal evaluation of prostate cancer foci in biopsies with discontinuous tumor involvement by dual ERG/SPINK1 immunohistochemistry.
abstract: The presence of two or more prostate cancer foci separated by intervening benign tissue in a single core is a well-recognized finding on prostate biopsy. Cancer involvement can be measured by including intervening benign tissue or only including the actual cancer involved area. Importantly, this parameter is a common enrollment criterion for active surveillance protocols. We hypothesized that spatially distinct prostate cancer foci in biopsies may arise from separate clones, impacting cancer involvement assessment. Hence, we used dual ERG/SPINK1 immunohistochemistry to determine the frequency of separate clones-when separate tumor foci showed discordant ERG and/or SPINK1 status-in discontinuously involved prostate biopsy cores from two academic institutions. In our cohort of 97 prostate biopsy cores with spatially discrete tumor foci (from 80 patients), discontinuous cancer involvement including intervening tissue ranged from 20 to 100% and Gleason scores ranged from 6 to 9. Twenty-four (25%) of 97 discontinuously involved cores harbored clonally distinct cancer foci by discordant ERG and/or SPINK1 expression status: 58% (14/24) had one ERG(+) focus, and one ERG(-)/SPINK1(-) focus; 29% (7/24) had one SPINK1(+) focus and one ERG(-)/SPINK1(-) focus; and 13% (3/24) had one ERG(+) focus and one SPINK1(+) focus. ERG and SPINK1 overexpression were mutually exclusive in all tumor foci. In summary, our results show that ~25% of discontinuously involved prostate biopsy cores showed tumor foci with discordant ERG/SPINK1 status, consistent with multiclonal disease. The relatively frequent presence of multiclonality in discontinuously involved prostate biopsy cores warrants studies on the potential clinical impact of clonality assessment, particularly in cases where tumor volume in a discontinuous core may impact active surveillance eligibility.
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY, USA.|Englander Institute for Precision Medicine, Weill Medical College of Cornell University and New York-Presbyterian, New York, NY, USA.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Fontugne
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Kristina
authors.initials: K
authors.lastname: Davis
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Nallasivam
authors.initials: N
authors.lastname: Palanisamy
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Udager
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.|Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Rohit
authors.initials: R
authors.lastname: Mehra
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: McDaniel
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.|Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Javed
authors.initials: J
authors.lastname: Siddiqui
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY, USA.|Englander Institute for Precision Medicine, Weill Medical College of Cornell University and New York-Presbyterian, New York, NY, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rubin
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY, USA.|Englander Institute for Precision Medicine, Weill Medical College of Cornell University and New York-Presbyterian, New York, NY, USA.
authors.forename: Juan Miguel
authors.initials: JM
authors.lastname: Mosquera
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.|Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.|Department of Urology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Tomlins
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D062005:Biopsy, Large-Core Needle; D002352:Carrier Proteins / Q000032:analysis*; D002999:Clone Cells; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008824:Michigan; D060787:Neoplasm Grading; D009519:New York City; D011237:Predictive Value of Tests; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000473:pathology; D015534:Trans-Activators / Q000032:analysis*; D000071230:Transcriptional Regulator ERG; D014359:Trypsin Inhibitor, Kazal Pancreatic
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; C072312:ERG protein, human; C486642:SPINK1 protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D014359:Trypsin Inhibitor, Kazal Pancreatic