Journal
HUMAN PATHOLOGY
Volume 38, Issue 5, Pages 696-701Publisher
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1016/j.humpath.2006.11.012
Keywords
PSMA; prostate cancer; progression; tissue microarray (TMA)
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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,
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