Loss of phosphatase and tensin homolog expression is associated with recurrence and poor prognosis in patients with pancreatic ductal adenocarcinoma
Summary Phosphatase and tensin homolog (PTEN) is a tumor suppressor in the AKT/mTOR pathway. Animal model studies have shown that loss of PTEN function is involved in the progression of pancreatic cancer. However, the prognostic significance of loss of PTEN expression in pancreatic cancer is unclear...
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| Veröffentlicht in: | Human pathology 2013-06, Vol.44 (6), p.1024-1030 |
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| creator | Foo, Wai Chin, MD Rashid, Asif, MD, PhD Wang, Hua, MD, PhD Katz, Matthew H., MD Lee, Jeffrey E., MD Pisters, Peter W., MD Wolff, Robert A., MD Abbruzzese, James L., MD Fleming, Jason B., MD Wang, Huamin, MD, PhD |
| description | Summary Phosphatase and tensin homolog (PTEN) is a tumor suppressor in the AKT/mTOR pathway. Animal model studies have shown that loss of PTEN function is involved in the progression of pancreatic cancer. However, the prognostic significance of loss of PTEN expression in pancreatic cancer is unclear. PTEN expression was evaluated by immunohistochemistry on tissue microarrays consisting of multiple cores of 133 resected stage II pancreatic ductal adenocarcinomas. A PTEN expression score was calculated as the product of the percentage of positive tumor cells and the intensity of PTEN staining. We categorized PTEN expression for each tumor as retained (PTEN score >5) or lost (PTEN score ≤5). Thirty-four (25.6%) patients had tumors with loss of PTEN expression, and 99 (74.4%) had tumors with retained PTEN expression. Recurrence/Metastasis was observed in 88.2% (30/34) of patients whose tumors showed loss of PTEN compared with 68.7% (68/99) of patients whose tumors showed retained PTEN ( P = .03). Patients whose tumors showed loss of PTEN had a shorter overall survival (median, 19.9 ± 3.6 months) than did patients whose tumors had retained PTEN (32.7 ± 5.0 months, P = .03). In a multivariate analysis, loss of PTEN expression was an independent prognostic factor for poor overall survival in patients with stage II pancreatic ductal adenocarcinoma. No significant correlations between loss of PTEN expression and other clinicopathologic parameters were observed ( P > .05). Assessment of PTEN expression may be used as a prognostic marker for patients with resected pancreatic ductal adenocarcinoma. |
| doi_str_mv | 10.1016/j.humpath.2012.09.001 |
| format | Article |
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Animal model studies have shown that loss of PTEN function is involved in the progression of pancreatic cancer. However, the prognostic significance of loss of PTEN expression in pancreatic cancer is unclear. PTEN expression was evaluated by immunohistochemistry on tissue microarrays consisting of multiple cores of 133 resected stage II pancreatic ductal adenocarcinomas. A PTEN expression score was calculated as the product of the percentage of positive tumor cells and the intensity of PTEN staining. We categorized PTEN expression for each tumor as retained (PTEN score >5) or lost (PTEN score ≤5). Thirty-four (25.6%) patients had tumors with loss of PTEN expression, and 99 (74.4%) had tumors with retained PTEN expression. Recurrence/Metastasis was observed in 88.2% (30/34) of patients whose tumors showed loss of PTEN compared with 68.7% (68/99) of patients whose tumors showed retained PTEN ( P = .03). Patients whose tumors showed loss of PTEN had a shorter overall survival (median, 19.9 ± 3.6 months) than did patients whose tumors had retained PTEN (32.7 ± 5.0 months, P = .03). In a multivariate analysis, loss of PTEN expression was an independent prognostic factor for poor overall survival in patients with stage II pancreatic ductal adenocarcinoma. No significant correlations between loss of PTEN expression and other clinicopathologic parameters were observed ( P > .05). Assessment of PTEN expression may be used as a prognostic marker for patients with resected pancreatic ductal adenocarcinoma.</description><identifier>ISSN: 0046-8177</identifier><identifier>EISSN: 1532-8392</identifier><identifier>DOI: 10.1016/j.humpath.2012.09.001</identifier><identifier>PMID: 23260327</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor - analysis ; Carcinoma, Pancreatic Ductal - metabolism ; Carcinoma, Pancreatic Ductal - mortality ; Carcinoma, Pancreatic Ductal - pathology ; Chemotherapy ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoplasm Recurrence, Local - metabolism ; Neoplasm Recurrence, Local - mortality ; Neoplasm Recurrence, Local - pathology ; Pancreas ; Pancreatic cancer ; Pancreatic Neoplasms - metabolism ; Pancreatic Neoplasms - mortality ; Pancreatic Neoplasms - pathology ; Pathology ; Prognosis ; Proteins ; PTEN ; PTEN Phosphohydrolase - analysis ; PTEN Phosphohydrolase - biosynthesis ; Survival ; Tissue Array Analysis ; Tumors ; Young Adult</subject><ispartof>Human pathology, 2013-06, Vol.44 (6), p.1024-1030</ispartof><rights>Elsevier Inc.</rights><rights>2013 Elsevier Inc.</rights><rights>Copyright © 2013 Elsevier Inc. All rights reserved.</rights><rights>Copyright Elsevier Limited Jun 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c495t-24dc31403bcc9e8c70d47a49ce0f1a3e074944091f9423764b39b37753c690233</citedby><cites>FETCH-LOGICAL-c495t-24dc31403bcc9e8c70d47a49ce0f1a3e074944091f9423764b39b37753c690233</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0046817712003292$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23260327$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Foo, Wai Chin, MD</creatorcontrib><creatorcontrib>Rashid, Asif, MD, PhD</creatorcontrib><creatorcontrib>Wang, Hua, MD, PhD</creatorcontrib><creatorcontrib>Katz, Matthew H., MD</creatorcontrib><creatorcontrib>Lee, Jeffrey E., MD</creatorcontrib><creatorcontrib>Pisters, Peter W., MD</creatorcontrib><creatorcontrib>Wolff, Robert A., MD</creatorcontrib><creatorcontrib>Abbruzzese, James L., MD</creatorcontrib><creatorcontrib>Fleming, Jason B., MD</creatorcontrib><creatorcontrib>Wang, Huamin, MD, PhD</creatorcontrib><title>Loss of phosphatase and tensin homolog expression is associated with recurrence and poor prognosis in patients with pancreatic ductal adenocarcinoma</title><title>Human pathology</title><addtitle>Hum Pathol</addtitle><description>Summary Phosphatase and tensin homolog (PTEN) is a tumor suppressor in the AKT/mTOR pathway. Animal model studies have shown that loss of PTEN function is involved in the progression of pancreatic cancer. However, the prognostic significance of loss of PTEN expression in pancreatic cancer is unclear. PTEN expression was evaluated by immunohistochemistry on tissue microarrays consisting of multiple cores of 133 resected stage II pancreatic ductal adenocarcinomas. A PTEN expression score was calculated as the product of the percentage of positive tumor cells and the intensity of PTEN staining. We categorized PTEN expression for each tumor as retained (PTEN score >5) or lost (PTEN score ≤5). Thirty-four (25.6%) patients had tumors with loss of PTEN expression, and 99 (74.4%) had tumors with retained PTEN expression. Recurrence/Metastasis was observed in 88.2% (30/34) of patients whose tumors showed loss of PTEN compared with 68.7% (68/99) of patients whose tumors showed retained PTEN ( P = .03). Patients whose tumors showed loss of PTEN had a shorter overall survival (median, 19.9 ± 3.6 months) than did patients whose tumors had retained PTEN (32.7 ± 5.0 months, P = .03). In a multivariate analysis, loss of PTEN expression was an independent prognostic factor for poor overall survival in patients with stage II pancreatic ductal adenocarcinoma. No significant correlations between loss of PTEN expression and other clinicopathologic parameters were observed ( P > .05). Assessment of PTEN expression may be used as a prognostic marker for patients with resected pancreatic ductal adenocarcinoma.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biomarkers, Tumor - analysis</subject><subject>Carcinoma, Pancreatic Ductal - metabolism</subject><subject>Carcinoma, Pancreatic Ductal - mortality</subject><subject>Carcinoma, Pancreatic Ductal - pathology</subject><subject>Chemotherapy</subject><subject>Female</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Kaplan-Meier Estimate</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neoplasm Recurrence, Local - metabolism</subject><subject>Neoplasm Recurrence, Local - mortality</subject><subject>Neoplasm Recurrence, Local - pathology</subject><subject>Pancreas</subject><subject>Pancreatic cancer</subject><subject>Pancreatic Neoplasms - metabolism</subject><subject>Pancreatic Neoplasms - mortality</subject><subject>Pancreatic Neoplasms - pathology</subject><subject>Pathology</subject><subject>Prognosis</subject><subject>Proteins</subject><subject>PTEN</subject><subject>PTEN Phosphohydrolase - analysis</subject><subject>PTEN Phosphohydrolase - biosynthesis</subject><subject>Survival</subject><subject>Tissue Array Analysis</subject><subject>Tumors</subject><subject>Young Adult</subject><issn>0046-8177</issn><issn>1532-8392</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFks2O1DAQhC0EYoeFRwBZ4sIlwX9JxhfQasWfNBIH4Gx5nM7GQ2IHdwLse_DAOMoA0l44WbK-apermpCnnJWc8frlqeyXcbJzXwrGRcl0yRi_R3a8kqLYSy3ukx1jqi72vGkuyCPEUwZ4paqH5EJIUTMpmh35dYiINHZ06iNOvZ0tArWhpTME9IH2cYxDvKHwc0qA6GOgHqlFjM7bGVr6w889TeCWlCC4TTvFmOiU4k2ImOk8Jhv1EGbc8MkGlyBfOdoubrYDtS2E6GxyPsTRPiYPOjsgPDmfl-TL2zefr98Xh4_vPlxfHQqndDUXQrVOcsXk0TkNe9ewVjVWaQes41YCa5RWimneaSVkU6uj1EfZNJV0tWZCykvyYpubvX5bAGczenQwDDZAXNBwWUm1Z6LaZ_T5HfQUlxSyu5XiWohKV5mqNsqlHGuCzkzJjzbdGs7MWps5mXNtZq3NMG1yK1n37Dx9OY7Q_lX96SkDrzcAchzfPSSDzq95tz5nP5s2-v8-8erOBDf44J0dvsIt4L_fGMwa82ndnXV1uGDZgRbyN5Z_woU</recordid><startdate>20130601</startdate><enddate>20130601</enddate><creator>Foo, Wai Chin, MD</creator><creator>Rashid, Asif, MD, PhD</creator><creator>Wang, Hua, MD, PhD</creator><creator>Katz, Matthew H., MD</creator><creator>Lee, Jeffrey E., MD</creator><creator>Pisters, Peter W., MD</creator><creator>Wolff, Robert A., MD</creator><creator>Abbruzzese, James L., MD</creator><creator>Fleming, Jason B., MD</creator><creator>Wang, Huamin, MD, PhD</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><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></search><sort><creationdate>20130601</creationdate><title>Loss of phosphatase and tensin homolog expression is associated with recurrence and poor prognosis in patients with pancreatic ductal adenocarcinoma</title><author>Foo, Wai Chin, MD ; Rashid, Asif, MD, PhD ; Wang, Hua, MD, PhD ; Katz, Matthew H., MD ; Lee, Jeffrey E., MD ; Pisters, Peter W., MD ; Wolff, Robert A., MD ; Abbruzzese, James L., MD ; Fleming, Jason B., MD ; Wang, Huamin, MD, PhD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c495t-24dc31403bcc9e8c70d47a49ce0f1a3e074944091f9423764b39b37753c690233</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biomarkers, Tumor - analysis</topic><topic>Carcinoma, Pancreatic Ductal - metabolism</topic><topic>Carcinoma, Pancreatic Ductal - mortality</topic><topic>Carcinoma, Pancreatic Ductal - pathology</topic><topic>Chemotherapy</topic><topic>Female</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Kaplan-Meier Estimate</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Neoplasm Recurrence, Local - metabolism</topic><topic>Neoplasm Recurrence, Local - mortality</topic><topic>Neoplasm Recurrence, Local - pathology</topic><topic>Pancreas</topic><topic>Pancreatic cancer</topic><topic>Pancreatic Neoplasms - metabolism</topic><topic>Pancreatic Neoplasms - mortality</topic><topic>Pancreatic Neoplasms - pathology</topic><topic>Pathology</topic><topic>Prognosis</topic><topic>Proteins</topic><topic>PTEN</topic><topic>PTEN Phosphohydrolase - analysis</topic><topic>PTEN Phosphohydrolase - biosynthesis</topic><topic>Survival</topic><topic>Tissue Array Analysis</topic><topic>Tumors</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Foo, Wai Chin, MD</creatorcontrib><creatorcontrib>Rashid, Asif, MD, PhD</creatorcontrib><creatorcontrib>Wang, Hua, MD, PhD</creatorcontrib><creatorcontrib>Katz, Matthew H., MD</creatorcontrib><creatorcontrib>Lee, Jeffrey E., MD</creatorcontrib><creatorcontrib>Pisters, Peter W., MD</creatorcontrib><creatorcontrib>Wolff, Robert A., MD</creatorcontrib><creatorcontrib>Abbruzzese, James L., MD</creatorcontrib><creatorcontrib>Fleming, Jason B., MD</creatorcontrib><creatorcontrib>Wang, Huamin, MD, PhD</creatorcontrib><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><jtitle>Human pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Foo, Wai Chin, MD</au><au>Rashid, Asif, MD, PhD</au><au>Wang, Hua, MD, PhD</au><au>Katz, Matthew H., MD</au><au>Lee, Jeffrey E., MD</au><au>Pisters, Peter W., MD</au><au>Wolff, Robert A., MD</au><au>Abbruzzese, James L., MD</au><au>Fleming, Jason B., MD</au><au>Wang, Huamin, MD, PhD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Loss of phosphatase and tensin homolog expression is associated with recurrence and poor prognosis in patients with pancreatic ductal adenocarcinoma</atitle><jtitle>Human pathology</jtitle><addtitle>Hum Pathol</addtitle><date>2013-06-01</date><risdate>2013</risdate><volume>44</volume><issue>6</issue><spage>1024</spage><epage>1030</epage><pages>1024-1030</pages><issn>0046-8177</issn><eissn>1532-8392</eissn><abstract>Summary Phosphatase and tensin homolog (PTEN) is a tumor suppressor in the AKT/mTOR pathway. Animal model studies have shown that loss of PTEN function is involved in the progression of pancreatic cancer. However, the prognostic significance of loss of PTEN expression in pancreatic cancer is unclear. PTEN expression was evaluated by immunohistochemistry on tissue microarrays consisting of multiple cores of 133 resected stage II pancreatic ductal adenocarcinomas. A PTEN expression score was calculated as the product of the percentage of positive tumor cells and the intensity of PTEN staining. We categorized PTEN expression for each tumor as retained (PTEN score >5) or lost (PTEN score ≤5). Thirty-four (25.6%) patients had tumors with loss of PTEN expression, and 99 (74.4%) had tumors with retained PTEN expression. Recurrence/Metastasis was observed in 88.2% (30/34) of patients whose tumors showed loss of PTEN compared with 68.7% (68/99) of patients whose tumors showed retained PTEN ( P = .03). Patients whose tumors showed loss of PTEN had a shorter overall survival (median, 19.9 ± 3.6 months) than did patients whose tumors had retained PTEN (32.7 ± 5.0 months, P = .03). In a multivariate analysis, loss of PTEN expression was an independent prognostic factor for poor overall survival in patients with stage II pancreatic ductal adenocarcinoma. No significant correlations between loss of PTEN expression and other clinicopathologic parameters were observed ( P > .05). Assessment of PTEN expression may be used as a prognostic marker for patients with resected pancreatic ductal adenocarcinoma.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>23260327</pmid><doi>10.1016/j.humpath.2012.09.001</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Aged, 80 and over Biomarkers, Tumor - analysis Carcinoma, Pancreatic Ductal - metabolism Carcinoma, Pancreatic Ductal - mortality Carcinoma, Pancreatic Ductal - pathology Chemotherapy Female Humans Immunohistochemistry Kaplan-Meier Estimate Male Middle Aged Neoplasm Recurrence, Local - metabolism Neoplasm Recurrence, Local - mortality Neoplasm Recurrence, Local - pathology Pancreas Pancreatic cancer Pancreatic Neoplasms - metabolism Pancreatic Neoplasms - mortality Pancreatic Neoplasms - pathology Pathology Prognosis Proteins PTEN PTEN Phosphohydrolase - analysis PTEN Phosphohydrolase - biosynthesis Survival Tissue Array Analysis Tumors Young Adult |
| title | Loss of phosphatase and tensin homolog expression is associated with recurrence and poor prognosis in patients with pancreatic ductal adenocarcinoma |
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