Prostate-specific membrane antigen expression as a predictor of prostate cancer progression

Sven Perner, Matthias D. Hofer, Robert Kim, Rajal B. Shah, Haojie Li, Peter Möller, Richard E. Hautmann, Juergen E. Gschwend, Rainer Kuefer, Mark A. Rubin*

*Corresponding author for this work

Research output: Contribution to journalArticle

252 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)696-701
Number of pages6
JournalHuman pathology
Volume38
Issue number5
DOIs
StatePublished - May 1 2007

Keywords

  • PSMA
  • Progression
  • Prostate cancer
  • Tissue microarray (TMA)

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Perner, S., Hofer, M. D., Kim, R., Shah, R. B., Li, H., Möller, P., Hautmann, R. E., Gschwend, J. E., Kuefer, R., & Rubin, M. A. (2007). Prostate-specific membrane antigen expression as a predictor of prostate cancer progression. Human pathology, 38(5), 696-701. https://doi.org/10.1016/j.humpath.2006.11.012