{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T06:21:37Z","timestamp":1792304497923,"version":"4.4.0"},"reference-count":55,"publisher":"BMJ","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2010,1,11]]},"published-print":{"date-parts":[[2010,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Some uterine endometrioid adenocarcinomas exhibit a distinctive morphological phenotype characterised by the formation of microcystic, elongated and fragmented (MELF) glands. Immunohistochemical studies have suggested that MELF-type changes represent an epithelial\u2013mesenchymal transition which has been associated with\n                      <jats:italic>KRAS<\/jats:italic>\n                      activation in various tumours.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      To investigate the molecular characteristics of endometrial tumours showing MELF, with particular reference to the frequencies of\n                      <jats:italic>KRAS<\/jats:italic>\n                      and\n                      <jats:italic>BRAF<\/jats:italic>\n                      mutations and of microsatellite instability (MSI).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      MSI, and\n                      <jats:italic>KRAS<\/jats:italic>\n                      and\n                      <jats:italic>BRAF<\/jats:italic>\n                      mutation status, were assessed in 33 low-grade endometrial adenocarcinomas showing MELF features and the results compared with 33 control cases exhibiting a \u2018conventional\u2019 pattern of myometrial invasion. Standard histological parameters were also reviewed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Tumours with a MELF pattern of myometrial invasion showed more frequent vascular invasion and focal mucinous differentiation.\n                      <jats:italic>KRAS<\/jats:italic>\n                      mutations were more frequent in MELF positive than MELF negative tumours (45% vs 30%), but this difference was not statistically significant.\n                      <jats:italic>BRAF<\/jats:italic>\n                      mutations were not identified in any of the cases. MSI was identified in 20% of cases overall but did not correlate with the MELF phenotype.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Mutations in\n                      <jats:italic>KRAS<\/jats:italic>\n                      and\n                      <jats:italic>BRAF<\/jats:italic>\n                      genes are not directly implicated in the development of a MELF pattern of invasion in endometrial carcinoma. However, RAS-associated signalling pathways could be activated through other genetic or epigenetic mechanisms. The characterisation of such alterations may become increasingly important as novel therapies are developed that target mediators involved in tumour invasion.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jcp.2009.069500","type":"journal-article","created":{"date-parts":[[2010,6,30]],"date-time":"2010-06-30T05:46:07Z","timestamp":1277876767000},"page":"604-608","source":"Crossref","is-referenced-by-count":25,"title":["<i>KRAS<\/i>\n                    mutation and microsatellite instability in endometrial adenocarcinomas showing MELF-type myometrial invasion"],"prefix":"10.1136","volume":"63","author":[{"given":"C J R","family":"Stewart","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Amanuel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Grieu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Carrello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Iacopetta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2010,6,30]]},"reference":[{"key":"2025120518130937000_63.7.604.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)67063-8"},{"key":"2025120518130937000_63.7.604.2","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0b013e318162f690"},{"key":"2025120518130937000_63.7.604.3","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0463.2002.1101001.x"},{"key":"2025120518130937000_63.7.604.4","doi-asserted-by":"publisher","DOI":"10.1053\/hupa.2001.25929"},{"key":"2025120518130937000_63.7.604.5","doi-asserted-by":"crossref","first-page":"4783","DOI":"10.1200\/JCO.2006.06.7173","article-title":"Molecular and pathologic aspects of endometrial carcinogenesis","volume":"29","author":"Hecht","year":"2006","journal-title":"J Clin Oncol"},{"key":"2025120518130937000_63.7.604.6","doi-asserted-by":"publisher","DOI":"10.1080\/00313020601136153"},{"key":"2025120518130937000_63.7.604.7","doi-asserted-by":"crossref","unstructured":"Llobet D Pallares J Yeramian A . Molecular pathology of endometrial carcinoma; practical aspects from the diagnostic and therapeutical view points. J Clin Pathol. Published Online First: 31 October 2008. doi:10.1136\/jcp.2008.056101.","DOI":"10.1136\/jcp.2008.056101"},{"key":"2025120518130937000_63.7.604.8","doi-asserted-by":"publisher","DOI":"10.1002\/path.856"},{"key":"2025120518130937000_63.7.604.9","doi-asserted-by":"publisher","DOI":"10.1097\/01.pas.0000171001.87599.e2"},{"key":"2025120518130937000_63.7.604.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2007.05.022"},{"key":"2025120518130937000_63.7.604.11","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.2009.064949"},{"key":"2025120518130937000_63.7.604.12","doi-asserted-by":"publisher","DOI":"10.1097\/PGP.0b013e31818d8fe6"},{"key":"2025120518130937000_63.7.604.13","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-199901000-00007"},{"key":"2025120518130937000_63.7.604.14","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1827.2003.01509.x"},{"key":"2025120518130937000_63.7.604.15","doi-asserted-by":"crossref","unstructured":"Clement PB Young RH . Atlas of gynecologic surgical pathology. 2nd edn. Philadelphia: Elsevier Saunders, 2008:161\u00e2\u0080\u009393.","DOI":"10.1016\/B978-1-4160-2972-4.50012-X"},{"key":"2025120518130937000_63.7.604.16","doi-asserted-by":"publisher","DOI":"10.1097\/01.pgp.0000092161.33490.a9"},{"key":"2025120518130937000_63.7.604.17","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1080\/00313020903041135","article-title":"MELF pattern invasion in endometrial carcinoma: association with low-grade, myoinvasive endometrioid tumours, focal mucinous differentiation and vascular invasion","volume":"41","author":"Stewart","year":"2009","journal-title":"Pathology"},{"key":"2025120518130937000_63.7.604.18","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2009.03327.x"},{"key":"2025120518130937000_63.7.604.19","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2009.33"},{"key":"2025120518130937000_63.7.604.20","unstructured":"Stewart CJR Crook ML Doherty DA . Micro-anatomical variation in cellular proliferation in endometrial adenocarcinoma, and inverse correlation between Ki-67 and cytokeratin 7 expression. Histopathology (In press)."},{"key":"2025120518130937000_63.7.604.21","doi-asserted-by":"publisher","DOI":"10.1080\/00313020701329914"},{"key":"2025120518130937000_63.7.604.22","doi-asserted-by":"publisher","DOI":"10.1038\/nrc822"},{"key":"2025120518130937000_63.7.604.23","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21223"},{"key":"2025120518130937000_63.7.604.24","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2003.09.015"},{"key":"2025120518130937000_63.7.604.25","first-page":"1241","article-title":"Involvement of the ras genes in female genital tract cancer","volume":"26","author":"Mammas","year":"2005","journal-title":"Int J Oncol"},{"key":"2025120518130937000_63.7.604.26","doi-asserted-by":"publisher","DOI":"10.1515\/BC.2005.025"},{"key":"2025120518130937000_63.7.604.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2007.04.002"},{"key":"2025120518130937000_63.7.604.28","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.08.036"},{"key":"2025120518130937000_63.7.604.29","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-2670"},{"key":"2025120518130937000_63.7.604.30","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/86.16.1216"},{"key":"2025120518130937000_63.7.604.31","doi-asserted-by":"publisher","DOI":"10.1002\/1096-9896(2000)9999:9999<::AID-PATH769>3.0.CO;2-9"},{"key":"2025120518130937000_63.7.604.32","first-page":"252","article-title":"A rapid and non-isotopic method for the screening and sequencing of p53 gene mutations in formalin-fixed, paraffin-embedded tumors","volume":"10","author":"Soong","year":"1997","journal-title":"Mod Pathology"},{"key":"2025120518130937000_63.7.604.33","doi-asserted-by":"crossref","first-page":"566","DOI":"10.2144\/00283cr02","article-title":"Routine detection of the replication error phenotype in clinical tumor specimens using fluorescence-SSCP","volume":"28","author":"Iacopetta","year":"2000","journal-title":"Biotechniques"},{"key":"2025120518130937000_63.7.604.34","doi-asserted-by":"publisher","DOI":"10.1159\/000069311"},{"key":"2025120518130937000_63.7.604.35","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-5-2"},{"key":"2025120518130937000_63.7.604.36","doi-asserted-by":"publisher","DOI":"10.2353\/jmoldx.2009.090057"},{"key":"2025120518130937000_63.7.604.37","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1097\/00004347-199507000-00010","article-title":"Frequent occurrence of c-Ki-ras gene mutations in well differentiated endometrial adenocarcinoma showing infiltrative local growth with fibrosing stromal response","volume":"14","author":"Tsuda","year":"1995","journal-title":"Int J Gynecol Pathol"},{"key":"2025120518130937000_63.7.604.38","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(20000215)88:4<814::AID-CNCR12>3.0.CO;2-U"},{"key":"2025120518130937000_63.7.604.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2004.01.017"},{"key":"2025120518130937000_63.7.604.40","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.20702"},{"key":"2025120518130937000_63.7.604.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2005.09.029"},{"key":"2025120518130937000_63.7.604.42","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.21991"},{"key":"2025120518130937000_63.7.604.43","first-page":"1541","article-title":"Analysis of a correlation between the BRAF V600E mutation and abnormal DNA mismatch repair in patients with sporadic endometrial cancer","volume":"34","author":"Kawaguchi","year":"2009","journal-title":"Int J Onol"},{"key":"2025120518130937000_63.7.604.44","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2004.12.003"},{"key":"2025120518130937000_63.7.604.45","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-005-5296-8"},{"key":"2025120518130937000_63.7.604.46","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200109037"},{"key":"2025120518130937000_63.7.604.47","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2005.08.001"},{"key":"2025120518130937000_63.7.604.48","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdl455"},{"key":"2025120518130937000_63.7.604.49","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2008.38"},{"key":"2025120518130937000_63.7.604.50","first-page":"257","article-title":"KRAS mutations appear in the premalignant phase of both microsatellite stable and unstable endometrial carcinogenesis","volume":"52","author":"Mutter","year":"1999","journal-title":"J Clin Pathol: Mol Pathol"},{"key":"2025120518130937000_63.7.604.51","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(97)00154-8"},{"key":"2025120518130937000_63.7.604.52","doi-asserted-by":"publisher","DOI":"10.1006\/gyno.1998.5154"},{"key":"2025120518130937000_63.7.604.53","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(19990101)85:1<119::AID-CNCR17>3.0.CO;2-5"},{"key":"2025120518130937000_63.7.604.54","doi-asserted-by":"publisher","DOI":"10.1053\/j.semdp.2008.07.008"},{"key":"2025120518130937000_63.7.604.55","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1177\/107327480901600102","article-title":"The molecular biology of endometrial cancers and the implications for pathogenesis, classification, and targeted therapies","volume":"16","author":"Bansal","year":"2009","journal-title":"Cancer Control"}],"container-title":["Journal of Clinical Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jcp.2009.069500","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T02:13:22Z","timestamp":1764987202000},"score":1,"resource":{"primary":{"URL":"https:\/\/jcp.bmj.com\/lookup\/doi\/10.1136\/jcp.2009.069500"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,6,30]]},"references-count":55,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2010,6,30]]},"published-print":{"date-parts":[[2010,7]]}},"alternative-id":["10.1136\/jcp.2009.069500"],"URL":"https:\/\/doi.org\/10.1136\/jcp.2009.069500","relation":{},"ISSN":["0021-9746","1472-4146"],"issn-type":[{"value":"0021-9746","type":"print"},{"value":"1472-4146","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,6,30]]}}}