Dual-Color Fluorescence <i>In Situ</i> Hybridization Reveals an Association of Chromosome 8q22 but Not 8p21 Imbalance with High Grade Invasive Breast Carcinoma

<div><p>We previously reported molecular karyotype analysis of invasive breast tumour core needle biopsies by comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) (Walker et al, Genes Chromosomes Cancer, 2008 May;47(5):405-17). That study identified frequently recurring gains and losses involving chromosome bands 8q22 and 8p21, respectively. Moreover, these data highlighted an association between 8q22 gain and typically aggressive grade 3 tumors. Here we validate and extend our previous investigations through FISH analysis of tumor touch imprints prepared from excised breast tumor specimens. Compared to post-surgical tumor excisions, core needle biopsies are known to be histologically less precise when predicting tumor grade. Therefore investigating these chromosomal aberrations in tumor samples that offer more reliable pathological assessment is likely to give a better overall indication of association. A series of 60 breast tumors were screened for genomic copy number changes at 8q22 and 8p21 by dual-color FISH. Results confirm previous findings that 8p loss (39%) and 8q gain (74%) occur frequently in invasive breast cancer. Both absolute quantification of 8q22 gain across the sample cohort, and a separate relative assessment by 8q22:8p21 copy number ratio, showed that the incidence of 8q22 gain significantly increased with grade (p = 0.004, absolute and p = 0.02, relative). In contrast, no association was found between 8p21 loss and tumor grade. These findings support the notion that 8q22 is a region of interest for invasive breast cancer pathogenesis, potentially harboring one or more genes that, when amplified, precipitate the molecular events that define high tumor grade.</p></div

Relative copy number of 8q22 in 54 breast tumor touch preparations categorized by histological grade.

<p>Relative copy number for 8q22 was determined by calculating the mean copy number for RP11-10G10 (8q22) specific signals and dividing by the respective value for RP11-177H13 at 8p21. Copy number gain is scored positive by a ratio greater than 2.0.</p

Proportion of nuclei from 54 breast tumor touch preparations after FISH showing decreased copy number of BAC probe RP11-177H13 (8p21; black bars), and/or increased copy number of RP11-10G10 (8q22; gray bars).

<p>Copy number changes are marked as loss or gain if at least 10% (marked by dashed lines) of nuclei show less than 2 signals from RP11-177H13 or more than 2 signals from RP11-10G10. Tumors are sorted into three graphs according to histological grade.</p