Immunohistochemical expression of minichromosome maintenance complex protein 2 predicts biochemical recurrence in prostate cancer: a tissue microarray and digital imaging analysis–based study of 428 cases
Summary Prostate cancer remains a major health problem in the United States. Established clinicopathologic parameters such as Gleason score, T stage, and prostate-specific antigen levels are currently the guiding tools for prognostication and disease management. The addition of biomarkers could incr...
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| Veröffentlicht in: | Human pathology 2012-11, Vol.43 (11), p.1852-1865 |
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| creator | Toubaji, Antoun, MD Sutcliffe, Siobhan, PhD Chaux, Alcides, MD Lecksell, Kristen, BS Hicks, Jessica, MS De Marzo, Angelo M., MD, PhD Platz, Elizabeth A., ScD, MPH Netto, George J., MD |
| description | Summary Prostate cancer remains a major health problem in the United States. Established clinicopathologic parameters such as Gleason score, T stage, and prostate-specific antigen levels are currently the guiding tools for prognostication and disease management. The addition of biomarkers could increase the accuracy of these parameters for predicting disease progression, response to therapy, and survival. In this regard, the goal of this study was to evaluate minichromosome maintenance complex protein 2 and Ki-67 immunohistochemical expression as predictors of outcome in prostate cancer. For this purpose, 11 tissue microarrays were constructed using tumor and nontumor samples from 428 patients. Patients were divided into short-term (mean, 2.9 years) and long-term (mean, 14.1 years) follow-up groups. End points were biochemical recurrence for the short-term follow-up group and prostate cancer–related death for the long-term follow-up group. All men in the long-term follow-up group had biochemical recurrence at the time of recruitment. Expression of both markers was higher in tumor than in nontumor glands. Percentage of minichromosome maintenance complex protein 2 was associated with Gleason score in both groups. Percentage of Ki-67 was associated with Gleason score and pathologic stage only in the short-term follow-up group. Higher minichromosome maintenance complex protein 2 percentages were associated with biochemical recurrence in the short-term follow-up group. In the long-term follow-up group, neither minichromosome maintenance complex protein 2 nor Ki-67 levels predicted prostate cancer death. In conclusion, our results suggest that in patients treated by radical prostatectomy for clinically localized prostate cancer, immunohistochemistry for minichromosome maintenance complex protein 2 expression could be used to predict biochemical recurrence, independent of other known clinicopathologic factors. |
| doi_str_mv | 10.1016/j.humpath.2012.01.007 |
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Established clinicopathologic parameters such as Gleason score, T stage, and prostate-specific antigen levels are currently the guiding tools for prognostication and disease management. The addition of biomarkers could increase the accuracy of these parameters for predicting disease progression, response to therapy, and survival. In this regard, the goal of this study was to evaluate minichromosome maintenance complex protein 2 and Ki-67 immunohistochemical expression as predictors of outcome in prostate cancer. For this purpose, 11 tissue microarrays were constructed using tumor and nontumor samples from 428 patients. Patients were divided into short-term (mean, 2.9 years) and long-term (mean, 14.1 years) follow-up groups. End points were biochemical recurrence for the short-term follow-up group and prostate cancer–related death for the long-term follow-up group. All men in the long-term follow-up group had biochemical recurrence at the time of recruitment. Expression of both markers was higher in tumor than in nontumor glands. Percentage of minichromosome maintenance complex protein 2 was associated with Gleason score in both groups. Percentage of Ki-67 was associated with Gleason score and pathologic stage only in the short-term follow-up group. Higher minichromosome maintenance complex protein 2 percentages were associated with biochemical recurrence in the short-term follow-up group. In the long-term follow-up group, neither minichromosome maintenance complex protein 2 nor Ki-67 levels predicted prostate cancer death. In conclusion, our results suggest that in patients treated by radical prostatectomy for clinically localized prostate cancer, immunohistochemistry for minichromosome maintenance complex protein 2 expression could be used to predict biochemical recurrence, independent of other known clinicopathologic factors.</description><identifier>ISSN: 0046-8177</identifier><identifier>EISSN: 1532-8392</identifier><identifier>DOI: 10.1016/j.humpath.2012.01.007</identifier><identifier>PMID: 22554381</identifier><identifier>CODEN: HPCQA4</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Adenocarcinoma - metabolism ; Adenocarcinoma - mortality ; Adenocarcinoma - secondary ; Adenocarcinoma - therapy ; Adult ; Aged ; Antigens ; Biochemical recurrence ; Biological and medical sciences ; Biomarkers ; Biomarkers, Tumor - metabolism ; Cancer-specific death ; Cell Cycle Proteins - metabolism ; Cell growth ; Combined Modality Therapy ; Deoxyribonucleic acid ; Disease ; Disease Progression ; DNA ; Gynecology. Andrology. Obstetrics ; Humans ; Image Interpretation, Computer-Assisted ; Investigative techniques, diagnostic techniques (general aspects) ; Ki-67 ; Ki-67 Antigen - metabolism ; Laboratories ; Lymphatic Metastasis ; Male ; Male genital diseases ; MCM2 ; Medical sciences ; Middle Aged ; Minichromosome Maintenance Complex Component 2 ; Mortality ; Neoplasm Recurrence, Local - diagnosis ; Nephrology. Urinary tract diseases ; Nuclear Proteins - metabolism ; Open source software ; Pathology ; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques ; Patients ; Prognosis ; Prostate cancer ; Prostate-Specific Antigen - blood ; Prostatectomy ; Prostatic Neoplasms - metabolism ; Prostatic Neoplasms - mortality ; Prostatic Neoplasms - pathology ; Prostatic Neoplasms - therapy ; Proteins ; Scanners ; Statistical data ; Studies ; Survival analysis ; Survival Rate ; Tissue Array Analysis ; Tumors ; Tumors of the urinary system ; Urinary tract. Prostate gland</subject><ispartof>Human pathology, 2012-11, Vol.43 (11), p.1852-1865</ispartof><rights>Elsevier Inc.</rights><rights>2012 Elsevier Inc.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2012 Elsevier Inc. All rights reserved.</rights><rights>2012. Elsevier Inc.</rights><rights>2012 Elsevier Inc. All rights reserved. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c608t-642975d626809d9447ee951251e7376a63bfc985665f81620e0c7c8d82cd95f83</citedby><cites>FETCH-LOGICAL-c608t-642975d626809d9447ee951251e7376a63bfc985665f81620e0c7c8d82cd95f83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.humpath.2012.01.007$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26564933$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22554381$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Toubaji, Antoun, MD</creatorcontrib><creatorcontrib>Sutcliffe, Siobhan, PhD</creatorcontrib><creatorcontrib>Chaux, Alcides, MD</creatorcontrib><creatorcontrib>Lecksell, Kristen, BS</creatorcontrib><creatorcontrib>Hicks, Jessica, MS</creatorcontrib><creatorcontrib>De Marzo, Angelo M., MD, PhD</creatorcontrib><creatorcontrib>Platz, Elizabeth A., ScD, MPH</creatorcontrib><creatorcontrib>Netto, George J., MD</creatorcontrib><title>Immunohistochemical expression of minichromosome maintenance complex protein 2 predicts biochemical recurrence in prostate cancer: a tissue microarray and digital imaging analysis–based study of 428 cases</title><title>Human pathology</title><addtitle>Hum Pathol</addtitle><description>Summary Prostate cancer remains a major health problem in the United States. Established clinicopathologic parameters such as Gleason score, T stage, and prostate-specific antigen levels are currently the guiding tools for prognostication and disease management. The addition of biomarkers could increase the accuracy of these parameters for predicting disease progression, response to therapy, and survival. In this regard, the goal of this study was to evaluate minichromosome maintenance complex protein 2 and Ki-67 immunohistochemical expression as predictors of outcome in prostate cancer. For this purpose, 11 tissue microarrays were constructed using tumor and nontumor samples from 428 patients. Patients were divided into short-term (mean, 2.9 years) and long-term (mean, 14.1 years) follow-up groups. End points were biochemical recurrence for the short-term follow-up group and prostate cancer–related death for the long-term follow-up group. All men in the long-term follow-up group had biochemical recurrence at the time of recruitment. Expression of both markers was higher in tumor than in nontumor glands. Percentage of minichromosome maintenance complex protein 2 was associated with Gleason score in both groups. Percentage of Ki-67 was associated with Gleason score and pathologic stage only in the short-term follow-up group. Higher minichromosome maintenance complex protein 2 percentages were associated with biochemical recurrence in the short-term follow-up group. In the long-term follow-up group, neither minichromosome maintenance complex protein 2 nor Ki-67 levels predicted prostate cancer death. In conclusion, our results suggest that in patients treated by radical prostatectomy for clinically localized prostate cancer, immunohistochemistry for minichromosome maintenance complex protein 2 expression could be used to predict biochemical recurrence, independent of other known clinicopathologic factors.</description><subject>Adenocarcinoma - metabolism</subject><subject>Adenocarcinoma - mortality</subject><subject>Adenocarcinoma - secondary</subject><subject>Adenocarcinoma - therapy</subject><subject>Adult</subject><subject>Aged</subject><subject>Antigens</subject><subject>Biochemical recurrence</subject><subject>Biological and medical sciences</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Cancer-specific death</subject><subject>Cell Cycle Proteins - metabolism</subject><subject>Cell growth</subject><subject>Combined Modality Therapy</subject><subject>Deoxyribonucleic acid</subject><subject>Disease</subject><subject>Disease Progression</subject><subject>DNA</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Image Interpretation, Computer-Assisted</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Ki-67</subject><subject>Ki-67 Antigen - metabolism</subject><subject>Laboratories</subject><subject>Lymphatic Metastasis</subject><subject>Male</subject><subject>Male genital diseases</subject><subject>MCM2</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Minichromosome Maintenance Complex Component 2</subject><subject>Mortality</subject><subject>Neoplasm Recurrence, Local - diagnosis</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Nuclear Proteins - metabolism</subject><subject>Open source software</subject><subject>Pathology</subject><subject>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</subject><subject>Patients</subject><subject>Prognosis</subject><subject>Prostate cancer</subject><subject>Prostate-Specific Antigen - blood</subject><subject>Prostatectomy</subject><subject>Prostatic Neoplasms - metabolism</subject><subject>Prostatic Neoplasms - mortality</subject><subject>Prostatic Neoplasms - pathology</subject><subject>Prostatic Neoplasms - therapy</subject><subject>Proteins</subject><subject>Scanners</subject><subject>Statistical data</subject><subject>Studies</subject><subject>Survival analysis</subject><subject>Survival Rate</subject><subject>Tissue Array Analysis</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>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFk9-O1CAUxhujccfVR9CQGBNvZgRaKPVijdn4Z5NNvFCvCUNPp4xtqRy62bnzHXwvH8InkWbGHd0LvYLA7_s4cD6y7DGjK0aZfLFdtVM_mtiuOGV8RdmK0vJOtmAi50uVV_xutqC0kEvFyvIke4C4pZQxUYj72QnnQhS5Yovsx0XfT4NvHUZvW-idNR2B6zEAovMD8Q3p3eBsG3zv0fdAeuOGCIMZLBDr-7GDazIGH8ENhKcZ1M5GJGt39AtgpxBgViQowRhNTOrZI7wkhkSHOCVrZ4M3IZgdMUNNardxMcldbzZu2KQ10-3Q4c9v39cGoSYYp3o3l1hwldwQ8GF2rzEdwqPDeJp9fvvm0_n75eWHdxfnry-XVlIVl7LgVSlqyaWiVV0VRQlQCcYFgzIvpZH5urGVElKKRjHJKVBbWlUrbusqLeWn2dned5zWPdQWhhhMp8eQag077Y3Tf-8MrtUbf6XzkgmqWDJ4fjAI_usEGHXv0ELXmQH8hJqlVgleVcV81tNb6NZPIb0Fai6LUhaSqX9SyatQquLVTIk9lR4aMUBzUzKjes6V3upDrvScK02ZTrlKuid_3vdG9TtICXh2AAymljch9dbhkZNCFlWeJ-7VnoPUnSsHQaN1czJql1ISde3df0s5u-VguzmhpvsCO8DjrTUmjf44f4L5DzBOKeWlyH8BjwkI0Q</recordid><startdate>20121101</startdate><enddate>20121101</enddate><creator>Toubaji, Antoun, MD</creator><creator>Sutcliffe, Siobhan, PhD</creator><creator>Chaux, Alcides, MD</creator><creator>Lecksell, Kristen, BS</creator><creator>Hicks, Jessica, MS</creator><creator>De Marzo, Angelo M., MD, PhD</creator><creator>Platz, Elizabeth A., ScD, MPH</creator><creator>Netto, George J., 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><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20121101</creationdate><title>Immunohistochemical expression of minichromosome maintenance complex protein 2 predicts biochemical recurrence in prostate cancer: a tissue microarray and digital imaging analysis–based study of 428 cases</title><author>Toubaji, Antoun, MD ; Sutcliffe, Siobhan, PhD ; Chaux, Alcides, MD ; Lecksell, Kristen, BS ; Hicks, Jessica, MS ; De Marzo, Angelo M., MD, PhD ; Platz, Elizabeth A., ScD, MPH ; Netto, George J., MD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c608t-642975d626809d9447ee951251e7376a63bfc985665f81620e0c7c8d82cd95f83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adenocarcinoma - metabolism</topic><topic>Adenocarcinoma - mortality</topic><topic>Adenocarcinoma - secondary</topic><topic>Adenocarcinoma - therapy</topic><topic>Adult</topic><topic>Aged</topic><topic>Antigens</topic><topic>Biochemical recurrence</topic><topic>Biological and medical sciences</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Cancer-specific death</topic><topic>Cell Cycle Proteins - metabolism</topic><topic>Cell growth</topic><topic>Combined Modality Therapy</topic><topic>Deoxyribonucleic acid</topic><topic>Disease</topic><topic>Disease Progression</topic><topic>DNA</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>Image Interpretation, Computer-Assisted</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Ki-67</topic><topic>Ki-67 Antigen - metabolism</topic><topic>Laboratories</topic><topic>Lymphatic Metastasis</topic><topic>Male</topic><topic>Male genital diseases</topic><topic>MCM2</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Minichromosome Maintenance Complex Component 2</topic><topic>Mortality</topic><topic>Neoplasm Recurrence, Local - diagnosis</topic><topic>Nephrology. Urinary tract diseases</topic><topic>Nuclear Proteins - metabolism</topic><topic>Open source software</topic><topic>Pathology</topic><topic>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</topic><topic>Patients</topic><topic>Prognosis</topic><topic>Prostate cancer</topic><topic>Prostate-Specific Antigen - blood</topic><topic>Prostatectomy</topic><topic>Prostatic Neoplasms - metabolism</topic><topic>Prostatic Neoplasms - mortality</topic><topic>Prostatic Neoplasms - pathology</topic><topic>Prostatic Neoplasms - therapy</topic><topic>Proteins</topic><topic>Scanners</topic><topic>Statistical data</topic><topic>Studies</topic><topic>Survival analysis</topic><topic>Survival Rate</topic><topic>Tissue Array Analysis</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>Toubaji, Antoun, MD</creatorcontrib><creatorcontrib>Sutcliffe, Siobhan, PhD</creatorcontrib><creatorcontrib>Chaux, Alcides, MD</creatorcontrib><creatorcontrib>Lecksell, Kristen, BS</creatorcontrib><creatorcontrib>Hicks, Jessica, MS</creatorcontrib><creatorcontrib>De Marzo, Angelo M., MD, PhD</creatorcontrib><creatorcontrib>Platz, Elizabeth A., ScD, MPH</creatorcontrib><creatorcontrib>Netto, George J., 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><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Human pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Toubaji, Antoun, MD</au><au>Sutcliffe, Siobhan, PhD</au><au>Chaux, Alcides, MD</au><au>Lecksell, Kristen, BS</au><au>Hicks, Jessica, MS</au><au>De Marzo, Angelo M., MD, PhD</au><au>Platz, Elizabeth A., ScD, MPH</au><au>Netto, George J., MD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunohistochemical expression of minichromosome maintenance complex protein 2 predicts biochemical recurrence in prostate cancer: a tissue microarray and digital imaging analysis–based study of 428 cases</atitle><jtitle>Human pathology</jtitle><addtitle>Hum Pathol</addtitle><date>2012-11-01</date><risdate>2012</risdate><volume>43</volume><issue>11</issue><spage>1852</spage><epage>1865</epage><pages>1852-1865</pages><issn>0046-8177</issn><eissn>1532-8392</eissn><coden>HPCQA4</coden><abstract>Summary Prostate cancer remains a major health problem in the United States. Established clinicopathologic parameters such as Gleason score, T stage, and prostate-specific antigen levels are currently the guiding tools for prognostication and disease management. The addition of biomarkers could increase the accuracy of these parameters for predicting disease progression, response to therapy, and survival. In this regard, the goal of this study was to evaluate minichromosome maintenance complex protein 2 and Ki-67 immunohistochemical expression as predictors of outcome in prostate cancer. For this purpose, 11 tissue microarrays were constructed using tumor and nontumor samples from 428 patients. Patients were divided into short-term (mean, 2.9 years) and long-term (mean, 14.1 years) follow-up groups. End points were biochemical recurrence for the short-term follow-up group and prostate cancer–related death for the long-term follow-up group. All men in the long-term follow-up group had biochemical recurrence at the time of recruitment. Expression of both markers was higher in tumor than in nontumor glands. Percentage of minichromosome maintenance complex protein 2 was associated with Gleason score in both groups. Percentage of Ki-67 was associated with Gleason score and pathologic stage only in the short-term follow-up group. Higher minichromosome maintenance complex protein 2 percentages were associated with biochemical recurrence in the short-term follow-up group. In the long-term follow-up group, neither minichromosome maintenance complex protein 2 nor Ki-67 levels predicted prostate cancer death. In conclusion, our results suggest that in patients treated by radical prostatectomy for clinically localized prostate cancer, immunohistochemistry for minichromosome maintenance complex protein 2 expression could be used to predict biochemical recurrence, independent of other known clinicopathologic factors.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>22554381</pmid><doi>10.1016/j.humpath.2012.01.007</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adenocarcinoma - metabolism Adenocarcinoma - mortality Adenocarcinoma - secondary Adenocarcinoma - therapy Adult Aged Antigens Biochemical recurrence Biological and medical sciences Biomarkers Biomarkers, Tumor - metabolism Cancer-specific death Cell Cycle Proteins - metabolism Cell growth Combined Modality Therapy Deoxyribonucleic acid Disease Disease Progression DNA Gynecology. Andrology. Obstetrics Humans Image Interpretation, Computer-Assisted Investigative techniques, diagnostic techniques (general aspects) Ki-67 Ki-67 Antigen - metabolism Laboratories Lymphatic Metastasis Male Male genital diseases MCM2 Medical sciences Middle Aged Minichromosome Maintenance Complex Component 2 Mortality Neoplasm Recurrence, Local - diagnosis Nephrology. Urinary tract diseases Nuclear Proteins - metabolism Open source software Pathology Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques Patients Prognosis Prostate cancer Prostate-Specific Antigen - blood Prostatectomy Prostatic Neoplasms - metabolism Prostatic Neoplasms - mortality Prostatic Neoplasms - pathology Prostatic Neoplasms - therapy Proteins Scanners Statistical data Studies Survival analysis Survival Rate Tissue Array Analysis Tumors Tumors of the urinary system Urinary tract. Prostate gland |
| title | Immunohistochemical expression of minichromosome maintenance complex protein 2 predicts biochemical recurrence in prostate cancer: a tissue microarray and digital imaging analysis–based study of 428 cases |
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