DNA in situ hybridization (interphase cytogenetics) versus comparative genomic hybridization (CGH) in human cancer: detection of numerical and structural chromosome aberrations

DNA in situ hybridization techniques for cytogenetic analyses of human soli d cancers are nowadays widely used for diagnostic and research purposes. Th e advantage of this methodology is that it can be applied to cells in the i nterphase state, thereby circumventing the need for high-quality metaphase preparations for karyotypic evaluation. In situ hybridization (ISH) with ch romosome specific (peri)centromeric DNA probes, also termed "interphase cyt ogenetics", can be used to detect numerical changes, whereas comparative ge nomic hybridization (CGH) discloses chromosomal gains and losses, i.e. ampl ifications and deletions. We wanted to compare both methods in human solid tumors, and for this goal we evaluated ISH and CGH within a set of 20 selec ted prostatic adenocarcinomas, Chromosomes 7 and 8 were chosen for this ana lysis, since these chromosomes are frequently altered in prostate cancer. I SH with chromosome 7 and 8 specific centromeric DNA probes was applied to s tandard, formalin-fixed and paraffin-embedded, histological sections for nu merical chromosome analysis. CGH with DNA's, extracted from the same histol ogic area of the archival specimens, was used for screening of gains and lo sses of 7 and 8. ISH with centromeric probes distinguished a total of 26 nu merical aberrations of chromosome 7 and/or 8 in the set of 20 neoplasms. In the same set CGH revealed a total of 35 losses and gains. CGH alterations of 7 and 8 were seen in twenty-two of the 26 chromosomes (85%) that showed aberrations in the ISH analysis. Concordance between ISH and CGH was seen i n 11 (of 26; 42%) chromosomes. Eight chromosomes were involved in gains (5x #7, 3x#8), three in lasses (3x#8). This included both complete (3/11) and p artial (8/11) CGH confirmation of the numerical alteration. Partial CGH con firmation was defined as loss or gain of a chromosome arm with involvement of the centromeric region. In the majority of these cases it concerned a wh ole chromosome arm, mostly the long arm. We conclude that generally a Fair correlation was found between ISH and CGH in interphase preparations of a s eries of prostate cancers. However; when specified in detail, most of the n umerical ISH aberrations were only partly represented in the CGH analysis. On the one hand, it suggests that CGH does not adequately discriminate nume rical abnormalities, On the other hand, it likely implies that not all nume rical changes, as detected by interphase cytogenetics, are truly involving the whole chromosome. A part of these discrepancies might be caused by stru ctural mechanisms, most notably isochromosome formation.