Correlation of cytologic findings and chromosomal instability detected by fluorescence in situ hybridization in breast fine-needle aspiration specimens from women at high risk for breast cancer

Abstract

Cytologic evaluation of ductal lavage or random periareolar fine-needle aspiration (FNA) specimens has been proposed to improve risk stratification of women at high risk for breast cancer. However, cytologic assessment of morphologic changes is subjective. To assess the utility of fluorescence in situ hybridization (FISH) in the categorization of breast lesions, we prospectively evaluated 32 random periareolar FNA specimens from 27 women at high risk for breast cancer. Cytologic specimens were prepared using the thin preparation technique, and diagnoses were made on the basis of previously published criteria. Specimens were also evaluated by FISH for chromosomes 1, 8, 11, and 17. Monosomy was defined as the loss of one signal or both signals in 420% of cells, and polysomy was defined as the presence of Z3 signals in 46% of cells. Cytologic smears from seven invasive ductal carcinomas and nine benign breast specimens from women at low risk for breast cancer were included for comparison. In the high-risk group, cytologic findings were nonproliferative epithelium (NPE) in 16 cases and hyperplasia in 16 cases. Chromosomal aberrations were detected in 11 (69%) of 16 NPE cases, 14 (89%) of 16 hyperplasia cases, seven (100%) of seven carcinoma cases, and none of the low-risk cases. Highrisk cases had significantly more monosomy of chromosomes 1, 11, and 17 and polysomy of chromosome 8 compared to low-risk cases and significantly less polysomy of chromosomes 1, 8, 11, and 17 compared to patients with cancer. There were no significant differences in monosomy or polysomy of individual chromosomes or a combination of chromosomes between the NPE and hyperplasia groups. This study shows that aberrations of chromosome number are common in high-risk women irrespective of cytologic findings. Studies evaluating the association between specific patterns of chromosomal polysomy and progression to malignancy may be warranted.

Comparison of Ductal Lavage and Random Periareolar Fine Needle Aspiration as Tissue Acquisition Methods in Early Breast Cancer Prevention Trials

“…The RPFNA procedure is well tolerated among women participating in breast cancer prevention trials, and the risk of infections requiring oral antibiotics is reported to be <1% (6,7). In a prospective phase II chemoprevention trial, the compliance was very high, and 114 out of 119 patients returned for the second RPFNA (23).…”

“…Subjects with a previous history of breast cancer underwent the procedure in their intact opposite breast. The RPFNA procedure was done as previously described (6,7). In all women, four RPFNA passes were done two each at the 3 o'clock and 9 o'clock positions in each breast.…”

RsaI polymorphism of the ERβgene in women with endometriosis

“…Its action is mediated by intracellular receptors, which, with the binding of ligands, are translocated to the nucleus, where it activates gene transcription. There are two subtypes of estrogen receptors (ERα and ERβ); they exhibit distinct cell and tissue differentiation distributions (Sneige et al, 2006).…”

Genome-based versus gene-based theory of cancer: Possibleimplications for clinical practice

“…C-myc gene, located on chromosome 8, is still not established as a potential prognostic marker. However, polysomy of chromosome 8 occurs frequently in breast carcinoma, and its high copy number is associated with high malignancy grade (Bofin et al 2003;Sneige et al 2006) and could be used as prognostic parameter indicating shorter survival (Tagawa et al 2003). Determination of numerical aberration of chromosome 20 in breast cancer showed that polysomy of chromosome 20 was the most prevalent aberration (90%) and that patients with a highest level of polysomy showed the worst survival (Nakopoulou et al 2002).…”