Magi-Galluzzi Cristina, Isharwal Sudhir, Falzarano Sara M, Tsiatis Athanasios, Dee Anne, Maddala Tara, Knezevic Dejan, Febbo Phillip G, Lawrence Jeffrey, Klein Eric A
Department of Urology, Glickman Urology and Kidney Institute, Cleveland Clinic, Cleveland, OH; Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH.
Department of Urology, Glickman Urology and Kidney Institute, Cleveland Clinic, Cleveland, OH.
Urology. 2018 Nov;121:132-138. doi: 10.1016/j.urology.2018.07.018. Epub 2018 Aug 22.
To compare the ability of loss of phosphatase and tensin homolog (PTEN) and Genomic prostate score assay (GPS) in predicting the biochemical-recurrence (BCR) and clinical-recurrence (CR) after radical prostatectomy (RP) for clinically localized prostate cancer (PCa).
Three hundred seventy seven patients with and without CR were retrospectively selected by stratified cohort sampling design from RP database. PTEN status (by immunohistochemistry [IHC] and fluorescence in situ hybridization [FISH]) and GPS results were determined for RP specimens. BCR was defined as Prostate Specific Antigen (PSA) ≥ 0.2 ng/mL or initiation of salvage therapy for a rising PSA. CR was defined as local recurrence and/or distant metastases.
Baseline mean age, PSA, and GPS score for the cohort were 61.1 years, 8 ng/dL, and 32.8. PTEN loss was noted in 38% patients by FISH and 25% by IHC. The concordance between FISH and IHC for PTEN loss was 66% (Kappa coefficient 0.278; P < .001). On univariable analysis, loss of PTEN by FISH or IHC was associated with BCR and CR (P < .05). However, after adjusting for GPS results, PTEN loss was not a significant predictor for CR or BCR (P > .1). The GPS result remained strongly associated with CR and BCR after adjusting for PTEN status (P < .001). PTEN status and GPS results only weakly correlated. GPS was widely distributed regardless of PTEN status indicating the biological heterogeneity of PCa even in PTEN-deficient cases.
GPS is a significant predictor of aggressive PCa, independent of PTEN status. After adjustment for GPS results, PTEN was not independently associated with recurrence for PCa.
比较磷酸酶和张力蛋白同源物（PTEN）缺失与基因组前列腺评分检测（GPS）在预测临床局限性前列腺癌（PCa）根治性前列腺切除术（RP）后生化复发（BCR）和临床复发（CR）方面的能力。
采用分层队列抽样设计，从RP数据库中回顾性选取377例有或无CR的患者。对RP标本测定PTEN状态（通过免疫组织化学[IHC]和荧光原位杂交[FISH]）和GPS结果。BCR定义为前列腺特异性抗原（PSA）≥0.2 ng/mL或因PSA升高开始挽救性治疗。CR定义为局部复发和/或远处转移。
该队列的基线平均年龄、PSA和GPS评分分别为61.1岁、8 ng/dL和32.8。FISH检测显示38%的患者存在PTEN缺失，IHC检测显示25%的患者存在PTEN缺失。FISH和IHC检测PTEN缺失的一致性为66%（Kappa系数0.278；P <.001）。单因素分析显示，FISH或IHC检测的PTEN缺失与BCR和CR相关（P <.05）。然而，在调整GPS结果后，PTEN缺失不是CR或BCR的显著预测因素（P >.1）。调整PTEN状态后，GPS结果仍与CR和BCR密切相关（P <.001）。PTEN状态与GPS结果仅存在弱相关性。无论PTEN状态如何，GPS分布广泛，表明即使在PTEN缺陷病例中PCa也具有生物学异质性。
GPS是侵袭性PCa的重要预测指标，独立于PTEN状态。调整GPS结果后，PTEN与PCa复发无独立相关性。
