{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T17:38:33Z","timestamp":1791049113660,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2012,3,13]],"date-time":"2012-03-13T00:00:00Z","timestamp":1331596800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2012,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND:<\/jats:title><jats:p>The purpose of the current study was to describe pure and mixed fibrolamellar hepatocellular carcinoma (FL\u2010HCC).<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS:<\/jats:title><jats:p>Consecutive patients with pure and mixed FL\u2010HCC were identified from a central pathological review using Edmondson's criteria. Clinical, pathological, and epigenetic characteristics of patients who underwent curative surgery were evaluated. Overall and disease\u2010free survival as well as patterns of disease recurrence were examined. Methylation levels of L1 retrotransposon (<jats:italic>LINE\u20101<\/jats:italic>) repetitive elements and Ras association domain family 1A gene (<jats:italic>RASSF1<\/jats:italic>) promoter were also assessed using pyrosequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS:<\/jats:title><jats:p>Forty of 53 patients with a median age of 22 years (range, 9 years\u2010;65 years) met the criteria for analysis. Central pathological review found that 30 patients (75%) had pure and 10 patients (25%) had mixed FL\u2010HCC. Pure FL\u2010HCC typically occurred in patients aged &lt; 30 years. These patients often presented with lymph node metastasis at the time of diagnosis and frequently experienced extrahepatic recurrences (n = 16). Conversely, mixed FL\u2010HCC appeared to resemble to classic HCC, occurring in patients aged &gt; 40 years and frequently involving the liver as the primary site of disease recurrence. With a median follow\u2010up of 7.8 years, the median overall survival from the time of diagnosis in all patients was 6.4 years (range, 3.2 years\u201012 years). Multivariate analysis found that the risk of death was increased in patients with higher American Joint Committee on Cancer disease stages (<jats:italic>P<\/jats:italic> = .003) and those with mixed FL\u2010HCC (<jats:italic>P<\/jats:italic> = .03). Methylation analysis of <jats:italic>LINE\u20101<\/jats:italic> repetitive elements and <jats:italic>RASSF1<\/jats:italic> promoter revealed different methylation levels between pure and mixed FL\u2010HCC, suggesting a different epigenetic background.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS:<\/jats:title><jats:p>Pure and mixed FL\u2010HCC display distinct clinical presentations and epigenetic backgrounds leading to different prognoses and as such may be regarded as separate clinical entities. Cancer 2012. \u00a9 2012 American Cancer Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.27520","type":"journal-article","created":{"date-parts":[[2012,3,13]],"date-time":"2012-03-13T13:17:39Z","timestamp":1331644659000},"page":"4981-4990","source":"Crossref","is-referenced-by-count":45,"title":["Pure and mixed fibrolamellar hepatocellular carcinomas differ in natural history and prognosis after complete surgical resection"],"prefix":"10.1002","volume":"118","author":[{"given":"Gabriel G.","family":"Malouf","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Brugi\u00e8res","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010C\u00e9cile","family":"Le 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