Original contributionProstate-specific membrane antigen expression as a predictor of prostate cancer progression☆
Introduction
A randomized clinical trial comparing watchful waiting with radical prostatectomy demonstrated significant risk reduction in the development of metastatic disease and cancer-specific death in clinically localized prostate cancer. However, this study also suggests that 19 men require surgical treatment to prevent one clinical event [1]. Therefore, molecular biomarker discovery needs to focus on distinguishing aggressive prostate cancer requiring treatment from indolent disease that may be expectantly followed with the option of delayed treatment if needed. Distinct sets of genes and proteins have been identified to be associated with the progression from precursor lesions to localized disease and eventual hormone refractory metastatic disease [2]. Prostate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein [3], which is negatively regulated by androgen. PSMA is significantly overexpressed in androgen-independent prostate cancer [4]. Increased PSMA expression in prostate cancer is associated with higher tumor grade [5], [6] and a high risk of disease progression as defined by biochemical recurrence after radical prostatectomy [7].
Introduction of a more widespread prostate-specific antigen (PSA) screening has led to a dramatic increase in the identification of early localized prostate cancer. In areas of the world with less rigorous screening approaches, high-stage and metastatic prostate cancer represents a higher percentage of new cancer cases [8]. In a high-risk cohort with incomplete PSA screening, we analyzed PSMA expression to determine a potential clinical utility in the setting of high-risk prostate cancer treatment.
Section snippets
Patient population and tissue collection
This study included 450 patients with prostate cancer diagnosed at the University of Ulm Hospital, Ulm, Germany, between the years 1986 and 2000. For these men, we compared PSMA expression in different histopathologic categories (including 24 benign, 225 localized prostate cancer, 73 hormone-naïve lymph node metastases, and 128 hormone refractory distant metastases of different organ sites) [8], [9]. Among these, 93 men (63.4 years, 50.4-76.1 years [mean age, range]) who had localized and
Results
As listed in Table 1, the lowest mean z intensity of PSMA expression was found in benign prostate glands (upper third of core in Fig. 1A), followed by localized prostate adenocarcinoma (positive immunoreactive stained acinar cancer glands in lower two thirds of core in Fig. 1A) and hormone refractory distant metastases, and the highest PSMA expression was observed in the category of regional lymph node metastases (Fig. 1B). As demonstrated in Fig. 2, mean PSMA expression was significantly
Discussion
In prostate cancer, Gleason score is still one of the most reliable parameters in predicting progression of disease [14] but, in many studies, fails to predict disease outcome independently [15], [16], [17]. Even nomograms using Gleason score in combination with extent of biopsy core involvement, pretreatment serum PSA levels, and clinical stage fail to adequately identify all patients at risk of developing biochemical recurrence [18]. Thus, molecular prognostic biomarkers independently
References (29)
- et al.
Isolation and characterization of monoclonal antibodies specific for the extracellular domain of prostate specific membrane antigen
J Urol
(1998) - et al.
Comparison of anti–prostate-specific membrane antigen antibodies and other immunomarkers in metastatic prostate carcinoma
Urology
(2001) - et al.
Prostate-specific membrane antigen expression is greatest in prostate adenocarcinoma and lymph node metastases
Urology
(1998) - et al.
Prognostic factors in lymph node–positive prostate cancer
Urology
(2006) Histologic grading of prostate cancer: a perspective
Hum Pathol
(1992)- et al.
Quantitative determination of expression of the prostate cancer protein alpha-methylacyl-CoA racemase using automated quantitative analysis (AQUA): a novel paradigm for automated and continuous biomarker measurements
Am J Pathol
(2004) - et al.
Characterization and predictors of prostate specific antigen progression rates after radical retropubic prostatectomy
J Urol
(2000) - et al.
Predicting life expectancy in men with clinically localized prostate cancer
J Urol
(2006) - et al.
Upregulation of prostate-specific membrane antigen after androgen-deprivation therapy
Urology
(1996) - et al.
Radical prostatectomy versus watchful waiting in early prostate cancer
N Engl J Med
(2005)
Pathological and molecular mechanisms of prostate carcinogenesis: implications for diagnosis, detection, prevention, and treatment
J Cell Biochem
Expression of the prostate-specific membrane antigen
Cancer Res
Correlation of primary tumor prostate-specific membrane antigen expression with disease recurrence in prostate cancer
Clin Cancer Res
Androgen-independent prostate cancer is a heterogeneous group of diseases: lessons from a rapid autopsy program
Cancer Res
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2023, Acta Pharmaceutica Sinica BCitation Excerpt :Prostate-specific membrane antigen (PSMA) is a membrane-bound type II transmembrane glycoprotein that is 100–1000 times upregulated in >90% prostate cancer cells compared with the level in healthy prostatic epithelial cells. The expression level of PSMA is positively correlated with the stage of the disease and Gleason score, making PSMA an attractive target for PCa diagnosis, intraoperative navigation, and therapy21. To date, various probes targeting PSMA have been developed, and several PSMA-PET/CT tracers have been utilized in clinics for identification of PCa pre- or/and post-surgery; whereas, these probes are impractical for real-time intraoperative use22–25.
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This work was supported by a grant of the Deutsche Forschungsgemeinschaft (German Research Foundation) (DFG number PE1179/1-1, for S. Perner) and a Department of Defense Fellowship Award (PC030214, for M. D. Hofer).