Genomic homogeneity in fibrolamellar carcinomas

Background-Fibrolamellar carcinoma (FLC) is a variant of hepatocellular carcinoma (HCC) with distinctive clinical and histological features. To date there have been few studies on the genotypic aspects of FLC and no previous attempts have been made to use the arbitrarily primed-polymerase chain reaction (AF-FCR) technique to detect genetic alterations in this disease.Aim-The aim of this study was to assess the degree of genomic heterogeneity of FEC using the AP-PCR technique. Methods-A fetal of 50 tissue samples of primary and metastatic FLCs from seven patients were microdissected. AP-PCR amplification of each genomic DNA sample was carried out using two arbitrary primers.Results-DNA fingerprints of the primary FLCs and all their metastatic lesions (both synchronous and metachronous disease) were identical in an individual patient. The fingerprints were different between tumours of different patients. No evidence of intratumour heterogeneity was observed.Conclusions-Such genomic homogeneity in FLCs may explain their indolent growth. The absence of clonal evolution, which is present in other tumours (particularly HCCs), may explain the distinct behaviour in this tumour. The tumorigenic pathway and degree of somatic genomic changes in this disease may be less complex than in HCC

The Potential Role of Intraoperative Ultrasonography in the Surgical Treatment of Hilar Cholangiocarci noma

The role of intraoperative ultrasonography (IOU) in the surgical treatment of hilar cholangiocarcinoma was explored in twenty-two patients, 17 males and 5 females. The mean age was 55 years (range 36-78 years). Preoperative imaging studies included abdominal ultra-sonography and/or CT scan, and visceral angiography. Operations performed were segment III bypass in 18 patients, local resection of tumour in 2 and resection of tumour en bloc with left hepatectomy in 2. Interpretation of IOU in terms of vascular involvement by the tumour (as compared to angiography or operative findings) was correct in 21 patients; no vascular invasion in 20 and portal vein invasion in the remainder. One false negative result occurred in a patient whose IOU failed to show right hepatic artery encasement by the tumour. When compared to postoperative cholangiography or surgical specimen, IOU correctly demon-strated location and extent of the tumours in all but one patient who had incomplete tumour resection. IOU was also helpful in locating segment III duct for biliary bypass. The mean time used for IOU was 15.1 min (range 10-20 min.), and there was no procedure-related com-plication. When supplemented with operative exploration, IOU seems to be very useful in the assessment of the resectability of hilar cholangiocarcinoma

Genomic homogeneity in fibrolamellar carcinomas

BACKGROUND—Fibrolamellar carcinoma (FLC) is a variant of hepatocellular carcinoma (HCC) with distinctive clinical and histological features. To date there have been few studies on the genotypic aspects of FLC and no previous attempts have been made to use the arbitrarily primed-polymerase chain reaction (AP-PCR) technique to detect genetic alterations in this disease.
AIM—The aim of this study was to assess the degree of genomic heterogeneity of FLC using the AP-PCR technique.
METHODS—A total of 50 tissue samples of primary and metastatic FLCs from seven patients were microdissected. AP-PCR amplification of each genomic DNA sample was carried out using two arbitrary primers.
RESULTS—DNA fingerprints of the primary FLCs and all their metastatic lesions (both synchronous and metachronous disease) were identical in an individual patient. The fingerprints were different between tumours of different patients. No evidence of intratumour heterogeneity was observed.
CONCLUSIONS—Such genomic homogeneity in FLCs may explain their indolent growth. The absence of clonal evolution, which is present in other tumours (particularly HCCs), may explain the distinct behaviour in this tumour. The tumorigenic pathway and degree of somatic genomic changes in this disease may be less complex than in HCC.


Keywords: fibrolamellar carcinoma; hepatocellular carcinoma; DNA fingerprint; arbitrarily primed-polymerase chain reaction; laser capture microdissectio

Non-random chromosomal rearrangements in pancreatic cancer cell lines identified by spectral karyotyping

The molecular events involved in pancreatic cancer are becoming increasingly well characterized, with mutations in the dominant oncogene KRAS and the tumour suppressor genes TP53, CDKN2A and MADH4 being typically observed. However, other genetic abnormalities remain to be identified and molecular cytogenetics may be useful to detect chromosomal loci involved in recurrent rearrangements. We have used spectral karyotyping to characterize cytogenetic aberrations in a panel of 20 human pancreatic carcinoma cell lines and confirmed their identities by dual and triple color fluorescence in situ hybridization. The most common partial or whole-arm gains involved 5p, 7q, 12p, 1q, 7p, 5q, 9p, 9q and 11p. The most common partial or whole-arm losses affected 9p, 11q, 18q, 3p, 2q and 1p, as well as the short arms of the acrocentric chromosomes. Spectral karyotyping allowed us to identify a number of recurrent structural aberrations, all of them unbalanced: most frequently i(5)(p10), del(11)(q23), i(12)(p10), i(1)(q10), del(7)(q22) and del(10)(p11). Spectral karyotyping mapped the complex aberrations occurring in pancreatic cancer cell lines and identified non-random patterns of chromosomal rearrangement. This comprehensive characterization should be useful to direct future investigation. The observation that loss at 11q and gains at 5p with i(5)(p10) and 12p with i(12)(p10) are more frequent changes than previously reported would justify more intensive investigation of these chromosomal regions