{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T15:02:17Z","timestamp":1770822137969,"version":"3.50.1"},"reference-count":48,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2009,12,23]],"date-time":"2009-12-23T00:00:00Z","timestamp":1261526400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2010,1]]},"abstract":"<jats:p>Jang K\u2010S, Song Y S, Jang S\u2010H, Min K\u2010W, Na W, Jang S M, Jun Y J, Lee K H, Choi D &amp; Paik S S\u2028(2010) <jats:italic>Histopathology<\/jats:italic><jats:bold>56,<\/jats:bold> 229\u2013239<\/jats:p><jats:p> <jats:bold>Clinicopathological significance of nuclear PTEN expression in colorectal adenocarcinoma<\/jats:bold> <\/jats:p><jats:p><jats:bold>Aims:\u2002<\/jats:bold> Tumour suppressor phosphatase and tensin homologue (<jats:italic>PTEN<\/jats:italic>) is an important negative regulator for the PIP3\/Akt signalling pathway that promotes cell proliferation and inhibits apoptosis. Inactivation of <jats:italic>PTEN<\/jats:italic> by mutation, deletion and promoter hypermethylation has been demonstrated in a range of cancers. The aim was to investigate whether the loss of nuclear PTEN protein expression correlates with conventional clinicopathological parameters and patient survival.<\/jats:p><jats:p><jats:bold>Methods and results:\u2002<\/jats:bold> Immunohistochemistry staining for PTEN was performed on a tissue microarray of 19 samples of normal colonic mucosa, 14 adenomatous polyps, 482 adenocarcinomas and 56 metastatic lymph nodes. All 19 normal colonic mucosa samples (100%) were positive and 12 (85.7%) out of 14 adenomatous polyps were positive for PTEN. However, only 241 (50.0%) of the 482 colorectal adenocarcinomas and 26 (46.4%) of the 56 metastatic lymph nodes were positive for PTEN. Loss of PTEN expression was related to defective mismatch repair protein expression and colonic localization rather than rectal localization. On univariate survival analysis, patients with PTEN\u2212 adenocarcinoma revealed a poor overall and disease\u2010free survival (<jats:italic>P<\/jats:italic>\u2003=\u20030.030 and <jats:italic>P<\/jats:italic>\u2003=\u20030.046, respectively). On multivariate analysis, a significant difference was observed in patients with stage II cancer that was not observed in other stages.<\/jats:p><jats:p><jats:bold>Conclusions:\u2002<\/jats:bold> Nuclear PTEN expression gradually decrease during the normal\u2013adenoma\u2013adenocarcinoma\u2013metastasis sequence, which suggests an important role for PTEN in carcinogenesis. Moreover, loss of nuclear PTEN expression was a marker of poor clinical outcome in patients with stage II colorectal cancer.<\/jats:p>","DOI":"10.1111\/j.1365-2559.2009.03468.x","type":"journal-article","created":{"date-parts":[[2009,12,23]],"date-time":"2009-12-23T17:46:52Z","timestamp":1261590412000},"page":"229-239","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Clinicopathological significance of nuclear PTEN expression in colorectal adenocarcinoma"],"prefix":"10.1111","volume":"56","author":[{"given":"Ki\u2010Seok","family":"Jang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young Soo","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Si\u2010Hyong","family":"Jang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyueng\u2010Whan","family":"Min","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Woong","family":"Na","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Se Min","family":"Jang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young Jin","family":"Jun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kang Hong","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongho","family":"Choi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seung Sam","family":"Paik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,12,23]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5308.1943"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.22.13375"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81780-8"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(07)00493-9"},{"key":"e_1_2_7_6_2","first-page":"2551","article-title":"Regulation of Akt\/PKB activity, cellular growth, and apoptosis in prostate carcinoma cells by MMAC\/PTEN","volume":"59","author":"Davies MA","year":"1999","journal-title":"Cancer Res."},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(99)00206-1"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.6.599"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.18.10182"},{"key":"e_1_2_7_10_2","first-page":"811","article-title":"Homozygous deletion of the PTEN tumor suppressor gene in a subset of prostate adenocarcinomas","volume":"4","author":"Wang SI","year":"1998","journal-title":"Clin. Cancer Res."},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/1098-1004(200008)16:2<109::AID-HUMU3>3.0.CO;2-0"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64627-5"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004280100499"},{"key":"e_1_2_7_14_2","first-page":"1178","article-title":"Lack of PTEN expression in non\u2010small cell lung cancer could be related to promoter methylation","volume":"8","author":"Soria JC","year":"2002","journal-title":"Clin. Cancer Res."},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2005.02.018"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1053\/hupa.2002.124721"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0046-8177(00)80244-0"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1006273516976"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1097\/00042737-200203000-00015"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.0678"},{"key":"e_1_2_7_21_2","first-page":"2881","article-title":"Loss of PTEN promotes tumor development in malignant melanoma","volume":"63","author":"Stahl JM","year":"2003","journal-title":"Cancer Res."},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-0397"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.anndiagpath.2003.11.002"},{"key":"e_1_2_7_24_2","first-page":"4291","article-title":"Loss of PTEN expression in paraffin\u2010embedded primary prostate cancer correlates with high Gleason score and advanced stage","volume":"59","author":"McMenamin ME","year":"1999","journal-title":"Cancer Res."},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0597-64"},{"key":"e_1_2_7_26_2","first-page":"4049","article-title":"Colorectal carcinomas and PTEN\/MMAC1 gene mutations","volume":"7","author":"Dicuonzo G","year":"2001","journal-title":"Clin. Cancer Res."},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.2.283"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-2401-2"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1159\/000086981"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.08.127"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.11266"},{"key":"e_1_2_7_32_2","first-page":"1474","article-title":"Combined loss of PTEN and p27 expression is associated with tumor cell proliferation by Ki\u201067 and increased risk of recurrent disease in localized prostate cancer","volume":"9","author":"Halvorsen OJ","year":"2003","journal-title":"Clin. Cancer Res."},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1001\/archotol.127.12.1441"},{"key":"e_1_2_7_34_2","first-page":"389","article-title":"PTEN\u2010positive and phosphorylated\u2010Akt\u2010negative expression is a predictor of survival for patients with advanced endometrial carcinoma","volume":"14","author":"Uegaki K","year":"2005","journal-title":"Oncol. Rep."},{"key":"e_1_2_7_35_2","first-page":"1100","article-title":"Dysregulation of PTEN and protein kinase B is associated with glioma histology and patient survival","volume":"8","author":"Ermoian RP","year":"2002","journal-title":"Clin. Cancer Res."},{"key":"e_1_2_7_36_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.pai.0000213127.96590.2d"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-5659"},{"key":"e_1_2_7_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6604009"},{"key":"e_1_2_7_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209089"},{"key":"e_1_2_7_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.908"},{"key":"e_1_2_7_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.11.040"},{"key":"e_1_2_7_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64200-9"},{"key":"e_1_2_7_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/1235"},{"key":"e_1_2_7_44_2","first-page":"3605","article-title":"High incidence of breast and endometrial neoplasia resembling human Cowden syndrome in Pten+\/\u2212 mice","volume":"60","author":"Stambolic V","year":"2000","journal-title":"Cancer Res."},{"key":"e_1_2_7_45_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-4143"},{"key":"e_1_2_7_46_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgm186"},{"key":"e_1_2_7_47_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2003.04.060"},{"key":"e_1_2_7_48_2","first-page":"3455","article-title":"Hypermethylation of the hMLH1 promoter in colon cancer with microsatellite instability","volume":"58","author":"Cunningham JM","year":"1998","journal-title":"Cancer Res."},{"key":"e_1_2_7_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjsurg.2007.05.061"}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2559.2009.03468.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1365-2559.2009.03468.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T11:15:22Z","timestamp":1698664522000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2559.2009.03468.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,12,23]]},"references-count":48,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2010,1]]}},"alternative-id":["10.1111\/j.1365-2559.2009.03468.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1365-2559.2009.03468.x","archive":["Portico"],"relation":{},"ISSN":["0309-0167","1365-2559"],"issn-type":[{"value":"0309-0167","type":"print"},{"value":"1365-2559","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,12,23]]},"assertion":[{"value":"2009-12-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}