Cancer · 2012
Pure and mixed fibrolamellar hepatocellular carcinomas differ in natural history and prognosis after complete surgical resection.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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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
Аннотация
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.
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.