{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T21:12:52Z","timestamp":1780089172848,"version":"3.54.0"},"reference-count":41,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2008,1,7]],"date-time":"2008-01-07T00:00:00Z","timestamp":1199664000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2008,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND.<\/jats:title><jats:p>Early colorectal cancer (ECC) is curable by endoscopic local resection; however, 10% of patients with ECC exhibit lymph node (LN) metastasis. In the current study, accurate predictors for LN metastasis in patients with ECC were examined by using immunohistochemistry with the lymphatic endothelial hyaluronan receptor 1 (LYVE\u20101) antibody to discriminate between lymphatics and blood vessels.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS.<\/jats:title><jats:p>Colorectal tissue specimens obtained from 71 patients with ECC, including 28 patients with regional LN metastasis, were immunostained with antibodies against LYVE\u20101, \u03b2\u2010catenin, claudin\u20103, claudin\u20104, and cytokeratin. The significance of the histopathologic variables for LN metastasis in ECC was investigated on the basis of specific histopathologic parameters.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS.<\/jats:title><jats:p>Lymphatic invasion confirmed by LYVE\u20101 immunohistochemistry was observed mainly in the submucosal area around the primary tumor and rarely was observed in the tumor. Expression patterns of \u03b2\u2010catenin, claudin\u20103, and claudin\u20104 in cancer cells at the invasive front were irrelevant to LN status. Tumor size, depth of invasion, histologic tumor type, budding formation, and lymphatic invasion were statistically significant to LN status in univariate analysis; however, only 2 factors\u2014lymphatic invasion and budding formation at the invasive front\u2014were independent predictors of LN metastasis in ECC.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS.<\/jats:title><jats:p>LYVE\u20101 immunohistochemistry appeared to be a useful method for detecting lymphatics invaded by cancer cells, and detailed examination of the submucosa around the tumor may be important for predicting LN metastasis. When lymphatic invasion and budding formation are observed histopathologically in patients with ECC, additional therapy, such as adjuvant chemotherapy or a curative resection of the regional LN, may be required. Cancer 2008. \u00a9 2008 American Cancer Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.23248","type":"journal-article","created":{"date-parts":[[2008,1,7]],"date-time":"2008-01-07T12:24:13Z","timestamp":1199708653000},"page":"924-933","source":"Crossref","is-referenced-by-count":69,"title":["Histopathologic determinants of regional lymph node metastasis in early colorectal cancer"],"prefix":"10.1002","volume":"112","author":[{"given":"Yukio","family":"Ishikawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri","family":"Akishima\u2010Fukasawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinji","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshikiyo","family":"Akasaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Yokoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiharu","family":"Ishii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"and the Toho Study Group for Cancer Biological Behavior","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,2]]},"reference":[{"key":"e_1_2_5_2_2","volume-title":"TNM Classification of Malignant Tumors","author":"Sobin LH","year":"2002"},{"key":"e_1_2_5_3_2","first-page":"2601","article-title":"Colorectal adenomas and cancer\u2014pathologic relationships","volume":"50","author":"Fenoglio CM","year":"1982","journal-title":"Cancer"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.25.5.437"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gassur.2004.09.038"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1080\/00365520510015746"},{"key":"e_1_2_5_7_2","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1083\/jcb.144.4.789","article-title":"LYVE\u20101, a new homologue of the CD44 glycoprotein, is a lymph\u2010specific receptor for hyaluronan","volume":"22","author":"Banerji S","year":"1999","journal-title":"J Cell Biol"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.3880543"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-003-0950-8"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1309\/LJQ9G0X8KP17QXP3"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10517-005-0385-0"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2005.09.091"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24543"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2005.05.019"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19890901)64:5<1138::AID-CNCR2820640529>3.0.CO;2-A"},{"key":"e_1_2_5_16_2","volume-title":"World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Digestive System","author":"Hamilton SR","year":"2000"},{"key":"e_1_2_5_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19890201)63:3<539::AID-CNCR2820630323>3.0.CO;2-S"},{"key":"e_1_2_5_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(85)90333-6"},{"key":"e_1_2_5_19_2","first-page":"1035","article-title":"Early invasive colorectal carcinomas metastatic to the lymph node with attention to their nonpolypoid development","volume":"88","author":"Minamoto T","year":"1993","journal-title":"Am J Gastroenterol"},{"key":"e_1_2_5_20_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.04.022"},{"key":"e_1_2_5_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02660767"},{"key":"e_1_2_5_22_2","doi-asserted-by":"publisher","DOI":"10.1053\/ejso.2002.1254"},{"key":"e_1_2_5_23_2","first-page":"117","volume-title":"Gastrointestinal and Oesophageal Pathology","author":"Gannon B","year":"1989"},{"key":"e_1_2_5_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(19960915)78:6<1179::AID-CNCR3>3.0.CO;2-5"},{"key":"e_1_2_5_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/s005350070020"},{"key":"e_1_2_5_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02238588"},{"key":"e_1_2_5_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10350-004-6259-0"},{"key":"e_1_2_5_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjsurg.2005.03.012"},{"key":"e_1_2_5_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02050592"},{"key":"e_1_2_5_30_2","doi-asserted-by":"publisher","DOI":"10.1159\/000095086"},{"key":"e_1_2_5_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2006.02.013"},{"key":"e_1_2_5_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/dc.20633"},{"key":"e_1_2_5_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6690393"},{"key":"e_1_2_5_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/pros.20199"},{"key":"e_1_2_5_35_2","first-page":"231","article-title":"Molecular mechanisms leading to cell junction (cadherin) deficiency in invasive carcinomas","volume":"4","author":"Birchmeier W","year":"1993","journal-title":"Semin Cancer Biol"},{"key":"e_1_2_5_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/0959-8049(94)00393-J"},{"key":"e_1_2_5_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6601124"},{"key":"e_1_2_5_38_2","first-page":"4789","article-title":"Expression of E\u2010cadherin and \u03b2\u2010catenin in human non\u2010small cell lung cancer and the clinical significance","volume":"6","author":"Kase S","year":"2000","journal-title":"Clin Cancer Res"},{"key":"e_1_2_5_39_2","first-page":"6265","article-title":"Claudin\u20104 expression decreases invasiveness and metastatic potential of pancreatic cancer","volume":"63","author":"Michl P","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_5_40_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-005-0011-6"},{"key":"e_1_2_5_41_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-1036"},{"key":"e_1_2_5_42_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1525-1438.2006.00748.x"}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcncr.23248","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.23248","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T21:50:10Z","timestamp":1760305810000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.23248"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,2]]},"references-count":41,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2008,2,15]]}},"alternative-id":["10.1002\/cncr.23248"],"URL":"https:\/\/doi.org\/10.1002\/cncr.23248","archive":["Portico"],"relation":{},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"value":"0008-543X","type":"print"},{"value":"1097-0142","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,2]]}}}