Title | Prostate-specific membrane antigen expression as a predictor of prostate cancer progression. |
Publication Type | Journal Article |
Year of Publication | 2007 |
Authors | Perner S, Hofer MD, Kim R, Shah RB, Li H, Möller P, Hautmann RE, Gschwend JE, Kuefer R, Rubin MA |
Journal | Hum Pathol |
Volume | 38 |
Issue | 5 |
Pagination | 696-701 |
Date Published | 2007 May |
ISSN | 0046-8177 |
Keywords | Adenocarcinoma, Aged, Cohort Studies, Disease Progression, Humans, Immunohistochemistry, Lymphatic Metastasis, Male, Middle Aged, Paraffin Embedding, Prostate-Specific Antigen, Prostatic Neoplasms, Recurrence |
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. |
DOI | 10.1016/j.humpath.2006.11.012 |
Alternate Journal | Hum. Pathol. |
PubMed ID | 17320151 |