Prostate-specific membrane antigen expression as a predictor of prostate cancer progression
Summary 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...
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| Veröffentlicht in: | Human pathology 2007-05, Vol.38 (5), p.696-701 |
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| creator | Perner, Sven, MD Hofer, Matthias D., MD Kim, Robert Shah, Rajal B., MD Li, Haojie, MD, PhD Möller, Peter, MD Hautmann, Richard E., MD Gschwend, Juergen E., MD Kuefer, Rainer, MD Rubin, Mark A., MD |
| description | Summary 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_str_mv | 10.1016/j.humpath.2006.11.012 |
| format | Article |
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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.</description><identifier>ISSN: 0046-8177</identifier><identifier>EISSN: 1532-8392</identifier><identifier>DOI: 10.1016/j.humpath.2006.11.012</identifier><identifier>PMID: 17320151</identifier><identifier>CODEN: HPCQA4</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Adenocarcinoma - diagnosis ; Adenocarcinoma - pathology ; Aged ; Biological and medical sciences ; Cohort Studies ; Disease Progression ; Humans ; Immunohistochemistry ; Investigative techniques, diagnostic techniques (general aspects) ; Lymphatic Metastasis ; Male ; Medical sciences ; Middle Aged ; Multivariate analysis ; Nephrology. Urinary tract diseases ; Paraffin Embedding ; Pathology ; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques ; Progression ; Prostate cancer ; Prostate-Specific Antigen - analysis ; Prostatic Neoplasms - diagnosis ; Prostatic Neoplasms - pathology ; PSMA ; Recurrence ; Studies ; Survival analysis ; Tissue microarray (TMA) ; Tumors ; Tumors of the urinary system ; Urinary tract. Prostate gland</subject><ispartof>Human pathology, 2007-05, Vol.38 (5), p.696-701</ispartof><rights>Elsevier Inc.</rights><rights>2007 Elsevier Inc.</rights><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c445t-b67426198ac7c68635c354f872dfd319598892bfef281e2ea8d1792259a424503</citedby><cites>FETCH-LOGICAL-c445t-b67426198ac7c68635c354f872dfd319598892bfef281e2ea8d1792259a424503</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0046817706006678$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18716500$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17320151$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Perner, Sven, MD</creatorcontrib><creatorcontrib>Hofer, Matthias D., MD</creatorcontrib><creatorcontrib>Kim, Robert</creatorcontrib><creatorcontrib>Shah, Rajal B., MD</creatorcontrib><creatorcontrib>Li, Haojie, MD, PhD</creatorcontrib><creatorcontrib>Möller, Peter, MD</creatorcontrib><creatorcontrib>Hautmann, Richard E., MD</creatorcontrib><creatorcontrib>Gschwend, Juergen E., MD</creatorcontrib><creatorcontrib>Kuefer, Rainer, MD</creatorcontrib><creatorcontrib>Rubin, Mark A., MD</creatorcontrib><title>Prostate-specific membrane antigen expression as a predictor of prostate cancer progression</title><title>Human pathology</title><addtitle>Hum Pathol</addtitle><description>Summary 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.</description><subject>Adenocarcinoma - diagnosis</subject><subject>Adenocarcinoma - pathology</subject><subject>Aged</subject><subject>Biological and medical sciences</subject><subject>Cohort Studies</subject><subject>Disease Progression</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Lymphatic Metastasis</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Multivariate analysis</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Paraffin Embedding</subject><subject>Pathology</subject><subject>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</subject><subject>Progression</subject><subject>Prostate cancer</subject><subject>Prostate-Specific Antigen - analysis</subject><subject>Prostatic Neoplasms - diagnosis</subject><subject>Prostatic Neoplasms - pathology</subject><subject>PSMA</subject><subject>Recurrence</subject><subject>Studies</subject><subject>Survival analysis</subject><subject>Tissue microarray (TMA)</subject><subject>Tumors</subject><subject>Tumors of the urinary system</subject><subject>Urinary tract. Prostate gland</subject><issn>0046-8177</issn><issn>1532-8392</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkd9rFDEQx4NY2rPtn6AsiI-7ZvJ7X5RS1BYKCtYnH0IuO2lz3u6eyV6x_71ZbuHAF5_CwGe-M_kMIa-BNkBBvd80j_t-56bHhlGqGoCGAntBViA5qw1v2UuyolSo2oDWZ-RVzhtKAaSQp-QMNGcUJKzIz29pzJObsM479DFEX_XYr5MbsHLDFB9wqPDPLmHOcRwqlytXlaqLfhpTNYZSHPor7waPaa4fFvqCnAS3zXi5vOfkx-dP99c39d3XL7fXV3e1F0JO9VppwRS0xnntlVFcei5FMJp1oePQytaYlq0DBmYAGTrTgW4Zk60TTEjKz8nbQ26Z_XuPebKbcZ-GMtIC5cJoUEIUSh4oXzbOCYPdpdi79FwgOyu1G7sotbNSC2CL0tL3Zknfr3vsjl2LwwK8WwCXvduG4s7HfOTm-ZLOa348cFhcPEVMNvuIRVoXE_rJdmP87yof_knw2zjEMvQXPmM-_tpmZqn9Pt9_Pj9VJURpw_8CAdqr0A</recordid><startdate>20070501</startdate><enddate>20070501</enddate><creator>Perner, Sven, MD</creator><creator>Hofer, Matthias D., MD</creator><creator>Kim, Robert</creator><creator>Shah, Rajal B., MD</creator><creator>Li, Haojie, MD, PhD</creator><creator>Möller, Peter, MD</creator><creator>Hautmann, Richard E., MD</creator><creator>Gschwend, Juergen E., MD</creator><creator>Kuefer, Rainer, MD</creator><creator>Rubin, Mark A., MD</creator><general>Elsevier Inc</general><general>Elsevier</general><general>Elsevier Limited</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope></search><sort><creationdate>20070501</creationdate><title>Prostate-specific membrane antigen expression as a predictor of prostate cancer progression</title><author>Perner, Sven, MD ; Hofer, Matthias D., MD ; Kim, Robert ; Shah, Rajal B., MD ; Li, Haojie, MD, PhD ; Möller, Peter, MD ; Hautmann, Richard E., MD ; Gschwend, Juergen E., MD ; Kuefer, Rainer, MD ; Rubin, Mark A., MD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c445t-b67426198ac7c68635c354f872dfd319598892bfef281e2ea8d1792259a424503</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Adenocarcinoma - diagnosis</topic><topic>Adenocarcinoma - pathology</topic><topic>Aged</topic><topic>Biological and medical sciences</topic><topic>Cohort Studies</topic><topic>Disease Progression</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Lymphatic Metastasis</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Multivariate analysis</topic><topic>Nephrology. Urinary tract diseases</topic><topic>Paraffin Embedding</topic><topic>Pathology</topic><topic>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</topic><topic>Progression</topic><topic>Prostate cancer</topic><topic>Prostate-Specific Antigen - analysis</topic><topic>Prostatic Neoplasms - diagnosis</topic><topic>Prostatic Neoplasms - pathology</topic><topic>PSMA</topic><topic>Recurrence</topic><topic>Studies</topic><topic>Survival analysis</topic><topic>Tissue microarray (TMA)</topic><topic>Tumors</topic><topic>Tumors of the urinary system</topic><topic>Urinary tract. Prostate gland</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Perner, Sven, MD</creatorcontrib><creatorcontrib>Hofer, Matthias D., MD</creatorcontrib><creatorcontrib>Kim, Robert</creatorcontrib><creatorcontrib>Shah, Rajal B., MD</creatorcontrib><creatorcontrib>Li, Haojie, MD, PhD</creatorcontrib><creatorcontrib>Möller, Peter, MD</creatorcontrib><creatorcontrib>Hautmann, Richard E., MD</creatorcontrib><creatorcontrib>Gschwend, Juergen E., MD</creatorcontrib><creatorcontrib>Kuefer, Rainer, MD</creatorcontrib><creatorcontrib>Rubin, Mark A., MD</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><jtitle>Human pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Perner, Sven, MD</au><au>Hofer, Matthias D., MD</au><au>Kim, Robert</au><au>Shah, Rajal B., MD</au><au>Li, Haojie, MD, PhD</au><au>Möller, Peter, MD</au><au>Hautmann, Richard E., MD</au><au>Gschwend, Juergen E., MD</au><au>Kuefer, Rainer, MD</au><au>Rubin, Mark A., MD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prostate-specific membrane antigen expression as a predictor of prostate cancer progression</atitle><jtitle>Human pathology</jtitle><addtitle>Hum Pathol</addtitle><date>2007-05-01</date><risdate>2007</risdate><volume>38</volume><issue>5</issue><spage>696</spage><epage>701</epage><pages>696-701</pages><issn>0046-8177</issn><eissn>1532-8392</eissn><coden>HPCQA4</coden><abstract>Summary 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.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>17320151</pmid><doi>10.1016/j.humpath.2006.11.012</doi><tpages>6</tpages></addata></record> |
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| subjects | Adenocarcinoma - diagnosis Adenocarcinoma - pathology Aged Biological and medical sciences Cohort Studies Disease Progression Humans Immunohistochemistry Investigative techniques, diagnostic techniques (general aspects) Lymphatic Metastasis Male Medical sciences Middle Aged Multivariate analysis Nephrology. Urinary tract diseases Paraffin Embedding Pathology Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques Progression Prostate cancer Prostate-Specific Antigen - analysis Prostatic Neoplasms - diagnosis Prostatic Neoplasms - pathology PSMA Recurrence Studies Survival analysis Tissue microarray (TMA) Tumors Tumors of the urinary system Urinary tract. Prostate gland |
| title | Prostate-specific membrane antigen expression as a predictor of prostate cancer progression |
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