Fluorescence in situ hybridization performed on tissue sec-difficulty of culturing tumor cells and the frequent finding of tions can reveal chromosomal abnormalities related to histocomplex karyotypes with highly abnormal chromosomes. 1,2 pathological features. This technique was performed on serial Fluorescence in situ hybridization (FISH) is a powerful techfrozen sections from seven normal livers and 29 hepatocellunique that enables detection of specific chromosomal aberralar carcinomas (HCCs) using pericentromeric repeat-specific tions and may circumvent some drawbacks of conventional probes for chromosomes 1, 4, 6, 7, 8, 16, and 17. For each cytogenetics. When performed on interphase nuclei, it avoids HCC and each probe, the percentage of cells showing one, the need for culturing tumor cells, a step that may select cells two, or more than two signals was counted and compared with a growth advantage and a different genetic background. 3 with the distribution in the normal liver. According to these This technique has recently been adapted for use on frozen results, HCCs were categorized as monosomic, disomic, or or paraffin-embedded tissue sections; when it is performed polysomic (more than two signals) for the chromosome tested. with pericentromeric chromosome-specific DNA probes, it These data were compared with the main histopathological allows assessment of numerical chromosomal changes comcharacteristics of HCC. Chromosome gains were very combined with histological analysis. [4][5][6] Good correlations have mon, preferentially affecting chromosome 1 (23 of 27 cases, been found between FISH and conventional cytogenetics. 7 85%), chromosome 16 (16 of 27 cases, 59%), chromosome 7
Hepatocellular carcinoma (HCC) is the major primary ma-(16 of 29 cases, 55%), chromosome 6 (15 of 29 cases, 52%) lignant tumor of the liver. 8 In the western world, most HCCs and chromosome 8 (14 of 29 cases, 48%). Monosomy was arise in cirrhotic livers. 9 A multistep carcinogenesis process seen more rarely, affecting preferentially chromosome 16 is suggested because experimental data and human observa-(19%), chromosome 17 (14%), and chromosome 4 (10%). A tions have shown a link between HCC, regenerative masignificant correlation was observed between aneusomy of cronodules, and cirrhosis. 10,11 This stepwise evolution is chromosome 4 and tumor size (P รต .05) or the presence of compatible with a succession of cumulative genetic events. vascular embolism (P รต .05). In conclusion, chromosomal Attempts have been made to characterize chromosomal abgains are frequent genetic events in human HCC. A significant normalities in HCC. Karyotyping of primary HCC is difficult association between a gain in chromosome 4 and large tumor and thus far has been achieved only in limited cases. 12,13 size or vascular embolism suggests that this genetic abnormal-Therefore, most cytogenetic studies were conducted on huity is a late event in liver carcinogenesis. (HEPATOLOGY man HCC cell lines. 14,15 A more recent approach was to study 1997;26:1492-1498.) loss of heterozygosity (LOH) by restriction fragment length polymorphism (RFLP) analysis in DNA extracted from HCC Karyotypic analysis has provided valuable information on using highly polymorphic microsatellite markers. [16][17][18][19][20][21][22] Alchromosomal aberrations in a wide range of malignant disthough this technique is very powerful and sensitive, eneases, but conventional cytogenetic analysis is laborious and abling localization of putative tumor-suppressor genes or celtime-consuming. Furthermore, cytogenetic studies are parlular oncogenes, [23][24][25][26][27][28] it must focus on a predefined part of ticularly challenging in malignant solid tumors because of the a selected chromosome. Furthermore, it is unsuitable for detecting a chromosome gain, a drawback not present with FISH.