TY - JOUR
T1 - Assessment of MYC/PTEN Status by Gene-Protein Assay in Grade Group 2 Prostate Biopsies
AU - Salles, Daniela C.
AU - Vidotto, Thiago
AU - Faisal, Farzana A.
AU - Tosoian, Jeffrey J.
AU - Guedes, Liana B.
AU - Muranyi, Andrea
AU - Bai, Isaac
AU - Singh, Shalini
AU - Yan, Dongyao
AU - Shanmugam, Kandavel
AU - Lotan, Tamara L.
N1 - Funding Information:
Disclosures: T.L.L. has received research support from Roche Tissue Diagnostics (RTD) for this study and from DeepBio for unrelated studies. A.M., S.S., and K.S. are employees of Roche and hold stock in RTD. I.B. and D.Y. are employees of RTD.
Funding Information:
Supported in part by the Patrick Walsh Prostate Cancer Research Fund (T.L.L.), NIH / National Cancer Institute (NCI) Prostate SPORE P50CA58236 (T.L.L.); and NCI Cancer Center support grant 5P30CA006973-52 (T.L.L.).
Publisher Copyright:
© 2021 Association for Molecular Pathology and American Society for Investigative Pathology
PY - 2021/8
Y1 - 2021/8
N2 - 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.
AB - 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.
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U2 - 10.1016/j.jmoldx.2021.05.006
DO - 10.1016/j.jmoldx.2021.05.006
M3 - Article
C2 - 34062284
AN - SCOPUS:85110527108
SN - 1525-1578
VL - 23
SP - 1030
EP - 1041
JO - Journal of Molecular Diagnostics
JF - Journal of Molecular Diagnostics
IS - 8
ER -