{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T09:09:33Z","timestamp":1762160973625},"reference-count":28,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2012,9,10]],"date-time":"2012-09-10T00:00:00Z","timestamp":1347235200000},"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":[[2012,12]]},"abstract":"<jats:p>Hirota K, Wakisaka N, Sawada\u2010Kitamura S, Kondo S, Endo K, Tsuji A, Murono S &amp; Yoshizaki T \u2028(2012) <jats:italic>Histopathology<\/jats:italic>\u2028<jats:bold>Lymphangiogenesis in regional lymph nodes predicts nodal recurrence in pathological N0 squamous cell carcinoma of the tongue<\/jats:bold><\/jats:p><jats:p><jats:bold>Aims:\u2002<\/jats:bold> Cancer cells induce <jats:italic>de\u2010novo<\/jats:italic> lymphatic vessel growth within draining lymph nodes before they metastasize. The aim of this study was to retrospectively evaluate lymph node lymphangiogenesis before the establishment of nodal recurrence in squamous cell carcinoma (SCC) of the tongue.<\/jats:p><jats:p><jats:bold>Methods and results:\u2002<\/jats:bold> Surgical specimens from 28 patients with pT2\u2013T3N0M0 SCC of the tongue after local excision with supraomohyoid neck dissection were studied by immunohistochemistry. Intranodal lymphatic endothelium was highlighted by podoplanin staining to evaluate lymphatic vessel counts (LVCs). Primary tumour sections were examined for the expression of lymphangiogenic factors: vascular endothelial growth factor (VEGF)\u2010C and VEGF\u2010D. LVCs in regional lymph nodes were significantly increased in the cases with nodal recurrence (<jats:italic>P<\/jats:italic>\u2003=\u20030.0013). Simultaneous increases in VEGF\u2010C and VEGF\u2010D expression were significantly associated with both an increase in LVC in regional lymph nodes (<jats:italic>P<\/jats:italic>\u2003=\u20030.0001) and a decrease in the rate of survival without nodal recurrence (<jats:italic>P<\/jats:italic>\u2003=\u20030.016).<\/jats:p><jats:p><jats:bold>Conclusions:\u2002<\/jats:bold> Knowing the status of lymphangiogenesis in the regional pN0 lymph nodes in tongue cancer would help in predicting which patients will develop nodal recurrence. The use of a therapeutic approach which blocks lymphangiogenic factors, such as VEGF\u2010C and VEGF\u2010D, may be beneficial in suppressing the lymphatic spread of tongue cancer with intense intranodal lymphangiogenesis.<\/jats:p>","DOI":"10.1111\/j.1365-2559.2012.04341.x","type":"journal-article","created":{"date-parts":[[2012,6,6]],"date-time":"2012-06-06T17:51:08Z","timestamp":1339005068000},"page":"1065-1071","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Lymphangiogenesis in regional lymph nodes predicts nodal recurrence in pathological N0 squamous cell carcinoma of the tongue"],"prefix":"10.1111","volume":"61","author":[{"given":"Kyoko","family":"Hirota","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naohiro","family":"Wakisaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seiko","family":"Sawada\u2010Kitamura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoru","family":"Kondo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuhira","family":"Endo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akira","family":"Tsuji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigeyuki","family":"Murono","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomokazu","family":"Yoshizaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,9,10]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/hed.2880140504"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2005.06.018"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1020329411957"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0215(20010120)95:1<44::AID-IJC1008>3.0.CO;2-M"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-007-9082-y"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1288\/00005537-197207000-00017"},{"key":"e_1_2_6_8_2","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/S0030-6665(20)32999-6","article-title":"Nodal metastases and prognosis in carcinoma of the oral cavity","volume":"5","author":"DiTroia JF","year":"1972","journal-title":"Otolaryngol. Clin. North Am."},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00405-010-1215-1"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2008.12.012"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-03-0826"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.060761"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-004-5783-x"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6603445"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20041896"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-2977"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0603-669"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/84643"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/84635"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/94.11.819"},{"key":"e_1_2_6_21_2","first-page":"713","article-title":"Differential in\u2003vivo and in\u2003vitro expression of vascular endothelial growth factor (VEGF)\u2010C and VEGF\u2010D in tumors and its relationship to lymphatic metastasis in immunocompetent rats","volume":"63","author":"Krishnan J","year":"2003","journal-title":"Cancer Res."},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/ar.20736"},{"key":"e_1_2_6_23_2","first-page":"716","article-title":"Prognostic significance of vascular endothelial growth factor D in breast carcinoma with long\u2010term follow\u2010up","volume":"9","author":"Nakamura Y","year":"2003","journal-title":"Clin. Cancer Res."},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2004.tb03167.x"},{"key":"e_1_2_6_25_2","first-page":"22","volume-title":"TNM classification of malignant tumours","author":"Sobin LH","year":"2002"},{"key":"e_1_2_6_26_2","article-title":"Induction of lymphangiogenesis through vascular endothelial growth factor\u2010C\/vascular endothelial growth factor receptor 3 axis and its correlation with lymph node metastasis in nasopharyngeal carcinoma","author":"Wakisaka N","journal-title":"Oral Oncol."},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-05-021758"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2011.03840.x"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-1230"}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2559.2012.04341.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1365-2559.2012.04341.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,15]],"date-time":"2023-10-15T01:56:41Z","timestamp":1697335001000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2559.2012.04341.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,9,10]]},"references-count":28,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2012,12]]}},"alternative-id":["10.1111\/j.1365-2559.2012.04341.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1365-2559.2012.04341.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":[[2012,9,10]]},"assertion":[{"value":"2012-09-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}