Original Article
Modern Pathology (2009) 22, 134–141; doi:10.1038/modpathol.2008.178; published online 7 November 2008
Chromosomal changes in fibrolamellar hepatocellular carcinoma detected by array comparative genomic hybridization
Sanjay Kakar1,2, Xin Chen3, Coral Ho3, Lawrence J Burgart4, Vaibhav Sahai5, Somkid Dachrut6, Annoel Yabes1, Dhanpat Jain7 and Linda D Ferrell1
- 1Department of Pathology, University of California, San Francisco, CA, USA
- 2Department of Pathology, Veteran Affairs Medical Center, San Francisco, CA, USA
- 3Department of Biopharamaceutical Sciences, University of California, San Francisco, CA, USA
- 4Abbott NW Hospital, Minneapolis, MN, USA
- 5Department of Medicine, Mercy Hospital, Pittsburgh, PA, USA
- 6Khon Kaen University, Khon Kaen, Thailand
- 7Yale University, New Haven, CT, USA
Correspondence: Dr S Kakar, MD, Department of Anatomic Pathology, UCSF and VA Medical Centers, 4150 Clement Street, San Francisco, CA 94121, USA. E-mail: sanjay.kakar@ucsf.edu
Received 23 June 2008; Revised 23 September 2008; Accepted 29 September 2008; Published online 7 November 2008.
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.
Keywords:
chromosomal changes, CGH, fibrolamellar, hepatocellular, survival
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