{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T13:00:15Z","timestamp":1788872415038,"version":"build-2803163510"},"reference-count":29,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,1,23]],"date-time":"2014-01-23T00:00:00Z","timestamp":1390435200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Korea government","award":["2009-0064073"],"award-info":[{"award-number":["2009-0064073"]}]},{"name":"Korea government","award":["2012R1A1A2040866"],"award-info":[{"award-number":["2012R1A1A2040866"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Oral Pathology Medicine"],"published-print":{"date-parts":[[2014,7]]},"abstract":"\n Background<\/jats:title>\n \n Although several studies reported that distant metastasis occurs more frequently in the tumors of submandibular gland (\n SMG<\/jats:styled-content>\n ) than parotid gland (\n PG<\/jats:styled-content>\n ), why\n SMG<\/jats:styled-content>\n tumors preferentially metastasize to distant organs is not fully understood. We aimed to identify the differential tumor microenvironment for distant metastasis and possible underlying mechanisms.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We retrieved 27 cases of 1\u20134\u2010cm\u2010sized adenoid cystic carcinomas (\n ACC<\/jats:styled-content>\n s) arising from the\n PG<\/jats:styled-content>\n (\n n\u00a0<\/jats:italic>\n =\n \u00a0<\/jats:italic>\n 12) and\n SMG<\/jats:styled-content>\n (\n n\u00a0<\/jats:italic>\n =\n \u00a0<\/jats:italic>\n 15). c\u2010\n KIT<\/jats:styled-content>\n ,\n VEGF<\/jats:styled-content>\n \u2010R2, and\n CD<\/jats:styled-content>\n 31 staining were quantified by image\u2010based analysis to define the positive expression or tumor\u2010associated vessel areas in two representative sections per case. In addition, angiogenesis\u2010related genomic expression profiling was carried out to explore the underlying mechanism, which was confirmed by\n RT<\/jats:styled-content>\n \u2010\n PCR<\/jats:styled-content>\n and immunohistochemistry.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Earlier systemic dissemination within 2\u00a0years was detected exclusively in\n SMG ACC<\/jats:styled-content>\n s (5\/15). The area of tumor\u2010associated blood vessels was larger in\n SMG ACC<\/jats:styled-content>\n s than\n PG ACC<\/jats:styled-content>\n s, and\n ACC<\/jats:styled-content>\n s showing distant metastasis had greater blood vessel area than those without metastasis. Interestingly, normal\n SMG<\/jats:styled-content>\n had more blood vessels per area than\n PG<\/jats:styled-content>\n . Among angiogenesis\u2010related signals, the level of\n IL<\/jats:styled-content>\n \u20106 was significantly lower in\n SMG ACC<\/jats:styled-content>\n s than\n PG ACC<\/jats:styled-content>\n s. Moreover,\n IL<\/jats:styled-content>\n \u20106 expression decreased significantly in\n SMG ACC<\/jats:styled-content>\n s compared with that in normal\n SMG<\/jats:styled-content>\n , whereas it was up\u2010regulated in\n PG ACC<\/jats:styled-content>\n s.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n ACC<\/jats:styled-content>\n s in the\n SMG<\/jats:styled-content>\n microenvironment have more abundant tumor\u2010associated blood vessels than\n PG ACC<\/jats:styled-content>\n s, which may explain the higher risk of distant metastasis from\n SMG<\/jats:styled-content>\n tumors.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/jop.12155","type":"journal-article","created":{"date-parts":[[2014,1,23]],"date-time":"2014-01-23T09:29:21Z","timestamp":1390469361000},"page":"441-447","source":"Crossref","is-referenced-by-count":17,"title":["Comparison of adenoid cystic carcinomas arising from the parotid gland vs. the submandibular gland: focus on systemic metastasis and tumor\u2010associated blood vessels"],"prefix":"10.1111","volume":"43","author":[{"given":"Da\u2010Yong","family":"Shin","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery Samsung Medical Center Sungkyunkwan University School of Medicine Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyu\u2010Sun","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery Samsung Medical Center Sungkyunkwan University School of Medicine Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery Samsung Medical Center Sungkyunkwan University School of Medicine Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Eun","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery Samsung Medical Center Sungkyunkwan University School of Medicine Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heejei","family":"Yoon","sequence":"additional","affiliation":[{"name":"Institute for Refractory Cancer Research Samsung Medical Center Sungkyunkwan University School of Medicine Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young\u2010Hyeh","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Pathology Samsung Medical Center Sungkyunkwan University School of Medicine Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han\u2010Sin","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery Samsung Medical Center Sungkyunkwan University School of Medicine 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