{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T11:03:58Z","timestamp":1772881438650,"version":"3.50.1"},"reference-count":57,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2010,4,28]],"date-time":"2010-04-28T00:00:00Z","timestamp":1272412800000},"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":[[2010,5]]},"abstract":"<jats:p>Tretiakova M S, Shabani\u2010Rad M T, Guggisberg K, Hart J, Anders R A &amp; Gao Z\u2010h\u2028(2010) <jats:italic>Histopathology<\/jats:italic>\u2002<jats:bold>56,<\/jats:bold> 683\u2013693\u2028<jats:bold>Genomic and immunophenotypical differences between hepatocellular carcinoma with and without cirrhosis<\/jats:bold><\/jats:p><jats:p><jats:bold>Aims:\u2002<\/jats:bold> To compare the expression of genes involved in p53, Wnt\/\u03b2\u2010catenin, and retinoblastoma (Rb) 1 pathways between cirrhosis\u2010associated hepatocellular carcinoma (HCC\u2010C) and hepatocellular carcinoma arising in non\u2010cirrhotic liver (HCC\u2010NC).<\/jats:p><jats:p><jats:bold>Methods and results:\u2002<\/jats:bold> The gene expression profile was analysed using oligo\u2010DNA arrays, and then validated at protein level in a tissue microarray using immunohistochemistry. Compared with their background non\u2010neoplastic liver tissue, HCC\u2010C showed a significantly higher rate of p53, \u03b2\u2010catenin (protein only) and cyclin D1 expression, whereas HCC\u2010NC showed a significantly higher rate of p21<jats:sup>Waf1\/cip1<\/jats:sup> and p27<jats:sup>Kip1<\/jats:sup> expression. HCC\u2010C had a significantly higher rate of p53 expression and a significantly lower rate of p21<jats:sup>waf1\/cip1<\/jats:sup> expression than HCC\u2010NC. There was no statistically significant association between the expression of genetic markers and tumour histological grade, underlying aetiology, or lymphovascular invasion. Aberrant \u03b2\u2010catenin expression was more commonly seen in single tumours in comparison with multiple tumours. Increased p16<jats:sup>INK4<\/jats:sup> and p21<jats:sup>waf1\/cip1<\/jats:sup> expression was more commonly observed in large\u2010sized tumours (&gt;50\u2003mm) than small\u2010sized tumours.<\/jats:p><jats:p><jats:bold>Conclusions:\u2002<\/jats:bold> Alteration of the p53 pathway plays a more important role in the pathogenesis of HCC\u2010C, whereas alterations in cell cycle regulators p21<jats:sup>waf1\/cip1<\/jats:sup> and p27<jats:sup>Kip1<\/jats:sup> play a more important role in the pathogenesis of HCC\u2010NC.<\/jats:p>","DOI":"10.1111\/j.1365-2559.2010.03554.x","type":"journal-article","created":{"date-parts":[[2010,4,29]],"date-time":"2010-04-29T18:42:32Z","timestamp":1272566552000},"page":"683-693","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Genomic and immunophenotypical differences between hepatocellular carcinoma with and without cirrhosis"],"prefix":"10.1111","volume":"56","author":[{"given":"Maria S","family":"Tretiakova","sequence":"first","affiliation":[]},{"given":"Meer T","family":"Shabani\u2010Rad","sequence":"additional","affiliation":[]},{"given":"Kelly","family":"Guggisberg","sequence":"additional","affiliation":[]},{"given":"John","family":"Hart","sequence":"additional","affiliation":[]},{"given":"Robert A","family":"Anders","sequence":"additional","affiliation":[]},{"given":"Zu\u2010hua","family":"Gao","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2010,4,28]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.3322\/canjclin.55.2.74"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(87)80021-1"},{"key":"e_1_2_6_4_2","first-page":"146","article-title":"Hepatocellular carcinogenesis: recent advances and speculations","volume":"2","author":"Harris CC","year":"1990","journal-title":"Cancer Cells"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.17.6547"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510240108"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840180109"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.1996.tb01739.x"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-199311000-00004"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.09.014"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/105.1.65"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(89)91426-1"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(89)91427-3"},{"key":"e_1_2_6_14_2","first-page":"174","article-title":"Hepatocellular carcinoma developed in non\u2010cirrhotic livers","volume":"111","author":"Tabarin A","year":"1987","journal-title":"Arch. Pathol. Lab. Med."},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19881001)62:7<1414::AID-CNCR2820620729>3.0.CO;2-7"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2000.9033"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.3800449"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209547"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.11254"},{"key":"e_1_2_6_20_2","first-page":"165","volume-title":"World Health Organization classification of tumor. Pathology and genetics of tumors of the digestive system","author":"Hirohashi S","year":"2000"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/biostatistics\/4.2.249"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1530509100"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-03-0751"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/dc.20281"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/88.20.1442"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.10.9.1054"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.950170606"},{"key":"e_1_2_6_28_2","first-page":"6358","article-title":"p53 gene mutation spectrum in hepatocellular carcinoma","volume":"52","author":"Oda T","year":"1992","journal-title":"Cancer Res."},{"key":"e_1_2_6_29_2","first-page":"491","article-title":"Infrequent mutation of p53 gene in hepatitis B virus positive primary hepatocellular carcinomas","volume":"8","author":"Hosono S","year":"1993","journal-title":"Oncogene"},{"key":"e_1_2_6_30_2","first-page":"5520","article-title":"Aberrations of the tumor suppressor p53 and retinoblastoma genes in human hepatocellular carcinomas","volume":"51","author":"Murakami Y","year":"1991","journal-title":"Cancer Res."},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.1999.tb00054.x"},{"key":"e_1_2_6_32_2","first-page":"6185","article-title":"Selective targeting of p53 gene mutational hotspots in human cancers by etiologically defined carcinogens","volume":"51","author":"Puisieux A","year":"1991","journal-title":"Cancer Res."},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1007\/s005340050060"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3835(97)00352-2"},{"key":"e_1_2_6_35_2","first-page":"2085","article-title":"Activation of beta\u2010catenin during hepatocarcinogenesis in transgenic mouse models: relationship to phenotype and tumor grade","volume":"61","author":"Calvisi DF","year":"2001","journal-title":"Cancer Res."},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1515\/BC.2002.027"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/1096-9896(2000)9999:9999<::AID-PATH720>3.0.CO;2-3"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(20010701)92:1<136::AID-CNCR1301>3.0.CO;2-R"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205434"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.2169"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1590\/S0036-46652002000100007"},{"key":"e_1_2_6_42_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.1890440113"},{"key":"e_1_2_6_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/71600"},{"key":"e_1_2_6_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90186-4"},{"key":"e_1_2_6_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-437X(01)00263-5"},{"key":"e_1_2_6_46_2","first-page":"5389","article-title":"Hepatocellular carcinoma results from chronic cyclin D1 overexpression in transgenic mice","volume":"61","author":"Deane NG","year":"2001","journal-title":"Cancer Res."},{"key":"e_1_2_6_47_2","first-page":"3107","article-title":"Amplification and overexpression of the cyclin D1 gene in aggressive human hepatocellular carcinoma","volume":"54","author":"Nishida N","year":"1994","journal-title":"Cancer Res."},{"key":"e_1_2_6_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202359"},{"key":"e_1_2_6_49_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510250314"},{"key":"e_1_2_6_50_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v11.i29.4587"},{"key":"e_1_2_6_51_2","doi-asserted-by":"publisher","DOI":"10.1053\/hupa.2001.22747"},{"key":"e_1_2_6_52_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20709"},{"key":"e_1_2_6_53_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2007.01470.x"},{"key":"e_1_2_6_54_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510280320"},{"key":"e_1_2_6_55_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2559.2001.01188.x"},{"key":"e_1_2_6_56_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgl060"},{"key":"e_1_2_6_57_2","doi-asserted-by":"publisher","DOI":"10.2174\/1566524033479546"},{"key":"e_1_2_6_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206401"}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2559.2010.03554.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1365-2559.2010.03554.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T21:54:55Z","timestamp":1698702895000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2559.2010.03554.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,4,28]]},"references-count":57,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2010,5]]}},"alternative-id":["10.1111\/j.1365-2559.2010.03554.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1365-2559.2010.03554.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":[[2010,4,28]]},"assertion":[{"value":"2010-04-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}