{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T10:12:54Z","timestamp":1784196774890,"version":"3.55.0"},"reference-count":46,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2001,12,21]],"date-time":"2001-12-21T00:00:00Z","timestamp":1008892800000},"content-version":"vor","delay-in-days":142,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathology International"],"published-print":{"date-parts":[[2001,8]]},"abstract":"<jats:p>Here we report the case of a 50\u2010year\u2010old woman with adenocarcinoma of the colon, showing heterotopic ossification. The patient was referred to our hospital for investigation of anemia secondary to occult gastrointestinal blood loss. By colonoscopy, an irregular polypoid mass was found in the ascending colon. A biopsy of the lesion revealed moderately to poorly differentiated adenocarcinoma with heterotopic ossification. A right hemicolectomy was done and revealed areas of heterotopic bone within the tumor, but no ossification was evident in the metastatic lesions within the mesenteric lymph nodes. The formation of heterotopic bone in gastrointestinal tumors is rare and its exact mechanism is unknown. Immunohistochemical localization of bone morphogenetic proteins (BMP), known to be primary inducers of new bone formation, was determined. BMP\u20105 and \u20106 were prominent in the cytoplasm of tumor cells, and they stained weakly in osteoblast\u2010like cells adjacent to newly formed bone. Cytoplasmic staining for BMP\u20102 and \u20104 was weak in tumor cells, osteoblast\u2010like cells, and stromal fibroblast cells. BMP may play an important role in heterotopic ossification in colon adenocarcinoma.<\/jats:p>","DOI":"10.1046\/j.1440-1827.2001.01243.x","type":"journal-article","created":{"date-parts":[[2003,3,12]],"date-time":"2003-03-12T17:17:27Z","timestamp":1047489447000},"page":"643-648","source":"Crossref","is-referenced-by-count":57,"title":["Expression of bone morphogenetic proteins in colon carcinoma with heterotopic ossification"],"prefix":"10.1111","volume":"51","author":[{"given":"Nobuhiro","family":"Imai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuhiro","family":"Iwai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Setsuko","family":"Hatakeyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Matsuzaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshitake","family":"Kitagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shingo","family":"Kato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryota","family":"Hokari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Kawaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeaki","family":"Nagao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Miyahara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuro","family":"Itoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soichiro","family":"Miura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2001,12,21]]},"reference":[{"key":"e_1_2_5_2_2","first-page":"160","article-title":"\u00dcber Knochenbildung in Karzinomen.","volume":"93","author":"Plenge K.","year":"1955","journal-title":"Zentralblatt Allg Pathol."},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00284002"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.150.3698.893"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3201241"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1089\/dna.1993.12.871"},{"key":"e_1_2_5_7_2","first-page":"827","article-title":"Vgr\u20101\/BMP\u20106 induces osteoblastic differentiation of pluripotential mesenchymal cells.","volume":"6","author":"Gitelman SE","year":"1995","journal-title":"Cell Growth Differ."},{"key":"e_1_2_5_8_2","doi-asserted-by":"crossref","first-page":"2671","DOI":"10.1210\/endo.136.6.7750491","article-title":"The effects of bone morphogenetic protein\u20102, \u20104, and \u20106 on differentiation of rat osteoblast cells in vitro.","volume":"136","author":"Hughes FJ","year":"1995","journal-title":"Endocrinology"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.137.8.3401"},{"key":"e_1_2_5_10_2","doi-asserted-by":"crossref","first-page":"2820","DOI":"10.1210\/endo.138.7.5125","article-title":"Glucocorticoid\u2010induced differentiation of fetal rat calvarial osteoblasts is mediated by bone morphogenetic protein\u20106.","volume":"138","author":"Boden SC","year":"1997","journal-title":"Endocrinology"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.1999.14.4.483"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01606451"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.1994.tb01119.x"},{"key":"e_1_2_5_14_2","first-page":"1235","article-title":"Retinoic acid enhances expression of bone morphogenetic protein\u20102 human adenocarcinoma cell line (HSG\u2010S8).","volume":"38","author":"Hatakeyama S","year":"1996","journal-title":"Biochem. Mol. Biol. Int."},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01211202"},{"key":"e_1_2_5_16_2","first-page":"497","article-title":"Expression of bone morphogenetic proteins of human neoplastic epithelial cells.","volume":"42","author":"Hatakeyama S","year":"1997","journal-title":"Biochem. Mol. Biol. Int."},{"key":"e_1_2_5_17_2","first-page":"5815","article-title":"Bone morphogenetic protein\u20106 is a marker of serous acinar cell differentiation in normal and neoplastic human salivary gland.","volume":"59","author":"Heikinheimo KA","year":"1999","journal-title":"Cancer Res."},{"key":"e_1_2_5_18_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1827.1999.00991.x"},{"key":"e_1_2_5_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5107(00)70173-8"},{"key":"e_1_2_5_20_2","first-page":"653","article-title":"Zur Kenntnis der Stromaerkno: cherung in Karzinomen des Digestionstraktes.","volume":"36","author":"Hasegawa T.","year":"1923","journal-title":"Wein Klin. Wochenschr."},{"key":"e_1_2_5_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01296512"},{"key":"e_1_2_5_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(197610)38:4<1773::AID-CNCR2820380453>3.0.CO;2-K"},{"key":"e_1_2_5_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.6403986"},{"key":"e_1_2_5_24_2","doi-asserted-by":"crossref","first-page":"20 805","DOI":"10.1016\/S0021-9258(19)47133-0","article-title":"Purification and characterization of a unique osteoinductive factor from bovine bone.","volume":"264","author":"Benz HRM","year":"1989","journal-title":"J. Biol. Chem."},{"key":"e_1_2_5_25_2","doi-asserted-by":"crossref","first-page":"13 377","DOI":"10.1016\/S0021-9258(18)80003-5","article-title":"Purification and partial amino acid sequence of osteogenin, a protein initiating bone differentiation.","volume":"264","author":"Luyten FP","year":"1989","journal-title":"J. Biol. Chem."},{"key":"e_1_2_5_26_2","doi-asserted-by":"crossref","first-page":"13 198","DOI":"10.1016\/S0021-9258(19)38285-7","article-title":"Bovine osteogenic protein is composed of dimers of OP\u20101 and BMP\u20102A, two members of the transforming growth factor\u2010\u03b2 superfamily.","volume":"265","author":"Sampath TK","year":"1990","journal-title":"J. Biol. Chem."},{"key":"e_1_2_5_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.24.9484"},{"key":"e_1_2_5_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.6.2220"},{"key":"e_1_2_5_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02556122"},{"key":"e_1_2_5_30_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.113.3.681"},{"key":"e_1_2_5_31_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.22.8793"},{"key":"e_1_2_5_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.5650061215"},{"key":"e_1_2_5_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(05)80208-6"},{"key":"e_1_2_5_34_2","doi-asserted-by":"publisher","DOI":"10.1210\/mend-5-1-149"},{"key":"e_1_2_5_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.5650061216"},{"key":"e_1_2_5_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.24.9843"},{"key":"e_1_2_5_37_2","doi-asserted-by":"crossref","first-page":"20 352","DOI":"10.1016\/S0021-9258(19)88709-4","article-title":"Recombinant human osteogenic protein\u20101 (hOP\u20101) induces new bone formation in vivo with a specific activity comparable with natural bovine osteogenic protein and stimulates osteoblast proliferation and differentiation in vitro.","volume":"267","author":"Sampath TK","year":"1992","journal-title":"J. Biol. Chem."},{"key":"e_1_2_5_38_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1996.0411"},{"key":"e_1_2_5_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1992.427"},{"key":"e_1_2_5_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1097-0215(19990924)83:1<38::aid-ijc8>3.3.co;2-2"},{"key":"e_1_2_5_41_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1995.0010"},{"key":"e_1_2_5_42_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.273.5275.613"},{"key":"e_1_2_5_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(97)00203-7"},{"key":"e_1_2_5_44_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1998.9181"},{"key":"e_1_2_5_45_2","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.1999.14.7.1075"},{"key":"e_1_2_5_46_2","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1242\/dev.127.9.1971","article-title":"The concentric stricture of the developing gut is regulated by Sonic hedgehog derived from endodermal epithelium.","volume":"127","author":"Sukegawa A","year":"2000","journal-title":"Development"},{"key":"e_1_2_5_47_2","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1242\/dev.127.5.981","article-title":"BMPs are necessary for stomach gland formation in the chicken embryo: a study using vially induced BMP\u20102 and Noggin expression.","volume":"127","author":"Narita T","year":"2000","journal-title":"Development"}],"container-title":["Pathology International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1046%2Fj.1440-1827.2001.01243.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1046\/j.1440-1827.2001.01243.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T01:27:11Z","timestamp":1697506031000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1046\/j.1440-1827.2001.01243.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,8]]},"references-count":46,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2001,8]]}},"alternative-id":["10.1046\/j.1440-1827.2001.01243.x"],"URL":"https:\/\/doi.org\/10.1046\/j.1440-1827.2001.01243.x","archive":["Portico"],"relation":{},"ISSN":["1320-5463","1440-1827"],"issn-type":[{"value":"1320-5463","type":"print"},{"value":"1440-1827","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,8]]}}}