Risk Stratification of Prostate Cancer Through Quantitative Assessment of PTEN Loss (qPTEN)

Author(s):Show less -

Jamaspishvili, Tamara ^{[1, 2]} ; Patel, Palak G. ^{[1, 2]} ; Niu, Yi ^{[3, 4]} ; Vidotto, Thiago ^{[5, 1, 6]} ; Caven, Isabelle ^{[1, 2]} ; Livergant, Rachel ^{[1, 2]} ; Fu, Winnie ^{[1, 2]} ; Kawashima, Atsunari ^{[1, 2, 7]} ; How, Nathan ^{[1, 2]} ; Okello, John B. ^{[1, 2]} ; Guedes, Liana B. ^[8] ; Ouellet, Veronique ^{[9, 10]} ; Picanco, Clarissa ^[5] ; Koti, Madhuri ^{[1, 6, 11]} ; Reis, Rodolfo B. ^[12] ; Saad, Fred ^{[9, 10, 13]} ; Mes-Masson, Anne-Marie ^{[14, 9, 10]} ; Lotan, Tamara L. ^{[8, 15]} ; Squire, Jeremy A. ^[5] ; Peng, Yingwei P. ^{[3, 16, 17]} ; Siemens, D. Robert ^[11] ; Berman, David M. ^{[1, 2, 6]}

Affiliation:Show less -

^[1] Queens Canc Res Inst, Div Canc Biol & Genet, Kingston, ON K7L 3N6 - Canada

^[2] Queens Univ, Dept Pathol & Mol Med, Kingston, ON K7L 3N6 - Canada

^[3] Queens Canc Res Inst, Div Canc Care & Epidemiol, Kingston, ON K7L 3N6 - Canada

^[4] Dalian Univ Technol, Sch Math Sci, Dalian 116024, Liaoning - Peoples R China

^[5] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, BR-14049900 Ribeirao Preto - Brazil

^[6] Queens Univ, Biomed & Mol Sci, Kingston, ON K7L 2V7 - Canada

^[7] Osaka Univ, Grad Sch Med, Dept Urol, Suita, Osaka 5650871 - Japan

^[8] Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21287 - USA

^[9] Univ Montreal, Inst Canc Montreal, Montreal, PQ H2X 0A9 - Canada

^[10] Univ Montreal, Ctr Hosp, Ctr Rech, Montreal, PQ H2X 0A9 - Canada

^[11] Queens Univ, Urol, Kingston, ON K7L 2V7 - Canada

^[12] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Surg & Anat, BR-14048900 Ribeirao Preto - Brazil

^[13] Univ Montreal, Dept Surg, Montreal, PQ H2X 0A9 - Canada

^[14] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7 - Canada

^[15] Johns Hopkins Univ, Dept Oncol, Baltimore, MD 21287 - USA

^[16] Queens Univ, Dept Publ Hlth Sci, Kingston, ON K7L 3N6 - Canada

^[17] Queens Univ, Math & Stat, Kingston, ON K7L 3N6 - Canada

• Document type: Journal article
• Source: JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE; v. 112, n. 11, p. 1098-1104, NOV 2020.
• Web of Science Citations: 4

Abstract

Background: Phosphatase and tensin homolog (PTEN) loss has long been associated with adverse findings in early prostate cancer. Studies to date have yet to employ quantitative methods (qPTEN) for measuring of prognostically relevant amounts of PTEN loss in postsurgical settings and demonstrate its clinical application. Methods: PTEN protein levels were measured by immunohistochemistry in radical prostatectomy samples from training (n = 410) and validation (n = 272) cohorts. PTEN loss was quantified per cancer cell and per tissue microarray core. Thresholds for identifying clinically relevant PTEN loss were determined using log-rank statistics in the training cohort. Univariate (Kaplan-Meier) and multivariate (Cox proportional hazards) analyses on various subpopulations were performed to assess biochemical recurrence-free survival (BRFS) and were independently validated. All statistical tests were two-sided. Results: PTEN loss in more than 65% cancer cells was most clinically relevant and had statistically significant association with reduced BRFS in training (hazard ratio {[}HR] = 2.48, 95% confidence interval {[}CI] = 1.59 to 3.87; P < .001) and validation cohorts (HR = 4.22, 95% CI = 2.01 to 8.83; P < .001). The qPTEN scoring method identified patients who recurred within 5.4 years after surgery (P < .001). In men with favorable risk of biochemical recurrence (Cancer of the Prostate Risk Assessment - Postsurgical scores <5 and no adverse pathological features), qPTEN identified a subset of patients with shorter BRFS (HR = 5.52, 95% CI = 2.36 to 12.90; P < .001) who may be considered for intensified monitoring and/or adjuvant therapy. Conclusions: Compared with previous qualitative approaches, qPTEN improves risk stratification of postradical prostatectomy patients and may be considered as a complementary tool to guide disease management after surgery. (AU)

• FAPESP's process: 15/09111-5 - Investigation of Clinically Useful Genomic Biomarkers in Prostate Cancer
• Grantee: Jeremy Andrew Squire
• Support Opportunities: Regular Research Grants