Chromosomal changes in fibrolamellar hepatocellular carcinoma detected by array comparative genomic hybridization

Abstract

Fibrolamellar hepatocellular carcinoma is a rare subtype of hepatocellular carcinoma with distinct clinical and histological features, and better survival compared with conventional hepatocellular carcinoma in some but not all series. We performed a comparative genomic hybridization analysis on 11 fibrolamellar carcinomas and correlated the findings with clinicopathologic features and survival. Chromosomal imbalances were identified in six cases (55%), whereas the other five (45%) yielded normal results. The mean number of aberrations per case was 3.9 for all cases and 7.2 in abnormal cases. Among the six abnormal cases, gains or losses were observed at 3 loci in two cases, 7 loci in one case, 8 loci in two cases and 14 loci in one case. The most common abnormalities were observed in chromosomes 7, 8 and 18, with 7q gain in five cases and 7p gain in four cases. Aberrations associated with intermediate or advanced conventional hepatocellular carcinomas, including losses at 3q, 4q and 13q were identified in 17-33% of fibrolamellar carcinomas. There was no correlation of chromosomal changes with age, gender and tumor size. The 5-year survival among the six patients with no chromosomal abnormalities was 80% (4/5) compared with 33% (2/6) in patients with chromosomal abnormalities (P=0.1). In conclusion, fibrolamellar carcinomas show fewer chromosomal abnormalities compared with those reported in literature for conventional hepatocellular carcinoma. The most common abnormalities occur in chromosomes 7 and 8. Fibrolamellar carcinomas with chromosomal changes appear to behave more aggressively compared with cases with no cytogenetic abnormalities. The favorable outcome in some fibrolamellar carcinomas may be due to absent or low number of cytogenetic aberrations.

Genome and transcriptome profiling of fibrolamellar hepatocellular carcinoma demonstrates p53 and IGF2BP1 dysregulation

“…Also using conventional CGH arrays, Kakar et al . found chromosomal imbalances in 6 of 11 (55%) FL-HCC tumors [14]. Although genomic alterations were evident in all samples in our series, the results of Kakar are similar to our bimodal distribution of chromosomal abnormalities, with 9 of 17 primary tumors (53%) having more than 1,000 gene amplifications or deletions, and the remainder having fewer than 100.…”

Claudins and tricellulin in fibrolamellar hepatocellular carcinoma

“…Several novel emerging tumor markers are available in the diagnostics of HCC with varying value and prognostic significance [1,3,[16][17][18]. Previously, we described for the first time that cholangiocellular carcinoma (CCC) is characterized by high expression of tight junction (TJ) protein claudin (CLDN) 4 in contrast to cHCC [19], which was later confirmed by others [20,21].…”

Fibrolamellar Hepatocellular Carcinoma: Mechanistic Distinction From Adult Hepatocellular Carcinoma

“…discovered overexpression of MAPK, PI3K, RAS, and xenobiotic pathways in FL‐HCCs . Kakar and Wilkens compared CGH profiles of FL‐HCCs and other HCCs; they found that none of the pathways that are frequently mutated in typical HCC, such as TP53, Wnt/β‐catenin, or survivin, are mutated in FL‐HCC . Other genes that are overexpressed in FL‐HCC include aromatase, EGFR, anterior gradient 2, and certain neuroendocrine markers such as PCSK1, neurotensin, calcitonin, and DNER .…”