Aneuploidy of chromosome 8 as detected by interphase fluorescence in situ hybridization is a recurrent finding in primary and metastatic breast cancer

Abstract

Previous work from our laboratory demonstrated aneuploidy for several chromosomes by interphase fluorescence in situ hybridization (FISH) in a high proportion of breast cancer specimens. In the literature, only limited data are available concerning chromosome 8 anomalies in breast cancer. To determine chromosome 8 ploidy status in primary and metastatic specimens from 81 breast cancer patients, FISH analysis with a DNA probe recognizing chromosome 8 centromeres was performed. In all primary tumor specimens (n = 30), significant proportions of cells were aneuploid exhibiting gain of chromosome 8 copy numbers; in 75% of effusion specimens previously classified as malignant by cytology and/or FISH for various chromosomes (n = 40), cell populations aneuploid for chromosome 8 were detected; effusions previously classified non-malignant (n = 11) were diploid in 10 cases, whereas one specimen contained rare hyperdiploid cells. Among these cells complex chromosomal aneuploidy could be demonstrated by two-color FISH, suggesting malignancy. Trisomic and tetrasomic clones were predominant in the majority of samples, but a marked intratumor cytogenetic heterogeneity was observed in most cases. Primary tumors and corresponding positive axillary lymph nodes revealed similar distributions of chromosome 8 copy numbers, analogous to previous findings with other chromosomes. This implies that, by using suitable FISH probes after examination of the respective primary tumor, an efficient search for (micro)metastasis might be feasible.

Monosomy of chromosome 8 could be considered as a primary preneoplastic event in breast cancer: A preliminary study

“…Breast cancer has three tumor markers currently in clinical use for selecting patients and monitoring therapy, which are necessary for diagnosis or prognosis (19). Our findings show that aneusomy of chromosome 8 is a more frequent polysomy in IDC tissue, as previously reported (6,9,10,20). With respect to IPL, our results showed that monosomy occurred more frequently in this tissue.…”

Chromosomal imbalances in primary and metastatic pancreatic carcinoma as detected by interphase cytogenetics: basic findings and clinical aspects

“…In effusion specimens with no detectable aneuploidy by the standard signal scoring procedure (n = 15), 1-2 x 104 nuclei (corresponding to 200 fields with 50-100 cells) were screened for the occurrence of rare aneuploid cells (as detailed previously; Roka et al, 1998). This is a procedure potentially practicable in the routine setting as, when in situ hybridization is appropriately performed (our laboratory set a minimum standard at 90% hybridization efficiency), it does not take more than 30 min to screen >10 000 nuclei.…”

“…Gain of chromosomes 7 and 11 and loss of chromosome 18 are frequent findings by metaphase karyotyping in exocrine pancreatic tumours, thus providing the background for FISH analysis of these chromosomes. As chromosome 8 is frequently aberrant in primary and metastatic breast cancer (Roka et al, 1998) and plays a role in prostate cancer progression (Jenkins et al, 1997), we additionally selected a centromere-specific probe to this chromosome to analyse numerical aberrations of chromosome 8 and their potential significance for pancreatic cancer progression.…”

“…Finally, the potential impact of aneuploidy detection by FISH for the identification of pancreatic (micro-)metastatic cells in effusions was evaluated, using an approach previously performed in breast cancer effusions (Roka et al, 1998;Zojer et al, 1997).…”

Inferring tumor progression from genomic heterogeneity

“…Heterogeneity has also been frequently observed in the analysis of karyotypes in breast tumors from single patients (Teixeira et al 1995(Teixeira et al , 1996Hein et al 1997). Several studies have also reported genetic heterogeneity in solid breast tumors using fluorescent in situ hybridization (FISH) experiments on interphase nuclei (Fiegl et al 1995;Roka et al 1998;Farabegoli et al 2001). These experiments commonly report that a specific FISH probe measures different copy number signals in individual cancer cells from the same tumor.…”