Details

Autor(en) / Beteiligte

• Malouf, Gabriel G.
• Brugières, Laurence
• Le Deley, Marie‐Cécile
• Faivre, Sandrine
• Fabre, Monique
• Paradis, Valérie
• Aerts, Isabelle
• Le Tourneau, Christophe
• Dreyer, Chantal
• Branchereau, Sophie
• Belghiti, Jacques
• Raymond, Eric

Titel

Pure and mixed fibrolamellar hepatocellular carcinomas differ in natural history and prognosis after complete surgical resection

Ist Teil von

• Cancer, 2012-10, Vol.118 (20), p.4981-4990

Ort / Verlag

Hoboken: Wiley Subscription Services, Inc., A Wiley Company

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• BACKGROUND: The purpose of the current study was to describe pure and mixed fibrolamellar hepatocellular carcinoma (FL‐HCC). METHODS: Consecutive patients with pure and mixed FL‐HCC 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‐free survival as well as patterns of disease recurrence were examined. Methylation levels of L1 retrotransposon (LINE‐1) repetitive elements and Ras association domain family 1A gene (RASSF1) promoter were also assessed using pyrosequencing. RESULTS: Forty of 53 patients with a median age of 22 years (range, 9 years‐;65 years) met the criteria for analysis. Central pathological review found that 30 patients (75%) had pure and 10 patients (25%) had mixed FL‐HCC. Pure FL‐HCC typically occurred in patients aged < 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‐HCC appeared to resemble to classic HCC, occurring in patients aged > 40 years and frequently involving the liver as the primary site of disease recurrence. With a median follow‐up of 7.8 years, the median overall survival from the time of diagnosis in all patients was 6.4 years (range, 3.2 years‐12 years). Multivariate analysis found that the risk of death was increased in patients with higher American Joint Committee on Cancer disease stages (P = .003) and those with mixed FL‐HCC (P = .03). Methylation analysis of LINE‐1 repetitive elements and RASSF1 promoter revealed different methylation levels between pure and mixed FL‐HCC, suggesting a different epigenetic background. CONCLUSIONS: Pure and mixed FL‐HCC display distinct clinical presentations and epigenetic backgrounds leading to different prognoses and as such may be regarded as separate clinical entities. Cancer 2012. © 2012 American Cancer Society. In the current study, a central pathological review was undertaken in all patients with the primary diagnosis of fibrolamellar hepatocellular carcinoma (FL‐HCC) who underwent complete surgical resection at 3 reference surgical centers. The authors report that pure FL‐HCC demonstrated epigenetic patterns and clinical characteristics at diagnosis and follow‐up that differ from mixed FL‐HCC. In this study, mixed FL‐HCC was found to more closely resemble classic HCC both in terms of epigenetic features, clinical presentation, and outcome.