Abstract
This study leveraged a gene-protein assay to assess MYC and PTEN status at prostate cancer biopsy and examined the association with adverse outcomes after surgery. MYC gain and PTEN loss were simultaneously assessed by chromogenic in situ hybridization and immunohistochemistry, respectively, using 277 Grade Group 2 needle biopsies that were followed by prostatectomy. The maximal size of cribriform Gleason pattern 4 carcinoma (CRIB), the presence of intraductal carcinoma (IDC), and percentage of Gleason pattern 4 carcinoma at biopsy were also annotated. MYC gain or PTEN loss was present in 19% and 18% of biopsies, respectively, whereas both alterations were present in 9% of biopsies. Tumors with one or both alterations were significantly more likely to have non–organ-confined disease (NOCD) at radical prostatectomy. In logistic regression models, including clinical stage, tumor volume on biopsy, and presence of CRIB/IDC, cases with MYC gain and PTEN loss remained at higher risk for NOCD (odds ratio, 6.23; 95% CI, 1.74–24.55; P = 0.005). The area under the curve for a baseline model using CAPRA variables (age, prostate-specific antigen, percentage of core involvement, clinical stage) was increased from 0.68 to 0.69 with inclusion of CRIB/IDC status and to 0.75 with MYC/PTEN status. Dual MYC/PTEN status can be assessed in a single slide and is independently associated with increased risk of NOCD for Grade Group 2 biopsies.
Highlights
IntroductionRecent refinements of pathologic evaluation of prostate cancer, including identification of intraductal carcinoma, have improved our ability to identify aggressive tumors.2,3
From the Departments of Pathology,* Urology,y and Oncology,{ and Roche Tissue Diagnostics, Tucson, Arizona,x Johns Hopkins University School of Medicine, Baltimore, Maryland; and the Department of Urology,z University of Michigan, Ann Arbor, Michigan
In logistic regression models, including clinical stage, tumor volume on biopsy, and presence of CRIB/intraductal carcinoma (IDC), cases with MYC gain and PTEN loss remained at higher risk for noneorgan-confined disease (NOCD)
Summary
Recent refinements of pathologic evaluation of prostate cancer, including identification of intraductal carcinoma, have improved our ability to identify aggressive tumors.2,3 Another morphologic factor that emerged in recent studies is the presence of cribriform Gleason pattern 4 disease because it is associated with up-staging and worse prognosis after prostatectomy.3e6 In addition, a number of genomic, largely RNA-based biomarkers have been marketed for use in patients with intermediate-risk prostate cancer.. Another morphologic factor that emerged in recent studies is the presence of cribriform Gleason pattern 4 disease because it is associated with up-staging and worse prognosis after prostatectomy.3e6 In addition, a number of genomic, largely RNA-based biomarkers have been marketed for use in patients with intermediate-risk prostate cancer.7,8 Many of these add to clinicopathologic parameters for the prediction of adverse outcomes, they require considerable amounts of tissue (often 5 to 10 unstained slides from a biopsy block), are highly dependent on adequate RNA preservation (which can be unpredictable in formalin-fixed, paraffin-embedded [FFPE] tissue), and cost.
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