title: Prostate-specific membrane antigen expression as a predictor of prostate cancer progression.
abstract: Distinguishing aggressive prostate cancer from indolent disease represents an important clinical challenge, because current therapy may lead to overtreatment of men with limited disease. The prostate-specific membrane antigen (PSMA) is a membrane-bound glycoprotein that is highly restricted to the prostate. Previously, studies analyzing the expression of PSMA have found an up-regulation in correlation with prostate cancer, particularly in advanced cancer. This association is ideal for an application as a prognostic marker. In the current study, we characterized PSMA expression in a high-risk cohort and evaluated its potential use as predictive marker of prostate-specific antigen (PSA) recurrence. PSMA expression was analyzed by immunohistochemistry using tissue microarrays composed of tumor samples from 450 patients. Protein intensity was recorded using a semiautomated quantitative microscope system (ACIS II; Clarient Chromavision Medical Systems, San Juan Capistrano, CA). PSMA expression levels differed significantly (P < .001) between benign prostatic tissue, localized prostate cancer, and lymph node metastases. Dividing the cohort into high- and low-PSMA expressing cancers based on the median area of positive staining, we found that high PSMA levels were associated with significant increase of PSA recurrence (P = .004). This was independent of clinical parameters such as lymph node tumor burden (lymph node density, >20%; P < .001), extraprostatic extension (P = .017), seminal vesicle invasion (P < .001), and high Gleason score (8-10, P = .006). In a multivariate model, PSMA expression and metastases to pelvic lymph nodes were significantly associated with time to PSA recurrence (HR, 1.4; 95% confidence interval, 1.1-2.8, P = .017; and hazard ratio, 5; 95% confidence interval, 2.6-9.7, P < .001, respectively). In summary, PSMA is independently associated with PSA recurrence in a high-risk cohort and thus might provide insight into the additional use of adjuvant therapy. Validation on other cohorts is required.
authors.affiliation: Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Sven
authors.initials: S
authors.lastname: Perner
authors.forename: Matthias D
authors.initials: MD
authors.lastname: Hofer
authors.forename: Robert
authors.initials: R
authors.lastname: Kim
authors.forename: Rajal B
authors.initials: RB
authors.lastname: Shah
authors.forename: Haojie
authors.initials: H
authors.lastname: Li
authors.forename: Peter
authors.initials: P
authors.lastname: Möller
authors.forename: Richard E
authors.initials: RE
authors.lastname: Hautmann
authors.forename: Juergen E
authors.initials: JE
authors.lastname: Gschwend
authors.forename: Rainer
authors.initials: R
authors.lastname: Kuefer
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rubin
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000473:pathology; D000368:Aged; D015331:Cohort Studies; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D016612:Paraffin Embedding; D017430:Prostate-Specific Antigen / Q000032:analysis*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000473:pathology; D012008:Recurrence
chemical_list: D017430:Prostate-Specific Antigen