Cytogenetic changes in nonmalignant breast tissue

Abstract

Cytogenetic changes are common in breast cancer and have also been described in fibroadenomas and fibrocystic disease, but not in histologically normal breast tissue. Cytogenetic analysis was performed on nonmalignant breast tissue from benign breast lumps (n = 8), reduction mammoplasties (n = 31), and grossly nontumorous tissue from cancerous breasts (n = 84), using standard techniques and G-banding. All samples were reviewed histologically. Clonal chromosomal changes were found in three of eight benign breast tumors (38%). Of the reduction mammoplasties, 17 samples contained nonproliferative changes, and three of these (18%) showed a clonal deletion of 3p. No pathology was identified in the other 14 samples, of which one (7%) contained two clonal changes, apparently balanced translocations. Of nontumorous tissues from cancerous breasts, 15 (18%) showed clonal chromosomal abnormalities. Five of these samples were histologically normal. Two clones were identical to those found in the corresponding cancer. In 18 additional samples, single cells were detected with the same change as that seen in clones or single cells in the cancer. Only 4 of these 20 samples contained detectable cancer cells. Clonal abnormalities found in two or more samples included trisomies X, 7, and 20 and monosomies 19 and 18. Clonal changes were not significantly more frequent in proliferative than in nonproliferative lesions. The Icelandic BRCA2 founder mutation, 999del5, was detected in four samples, all histologically normal, two of which had clonal chromosomal abnormalities. In conclusion, clonal chromosomal changes are not infrequent in nonmalignant breast tissue and can be detected even in the absence of histological abnormalities.

Cytogenetic polyclonality of breast carcinomas: Association with Clinico‐Pathological Characteristics and Outcome

“…It was also shown that chromosomal instability was significantly associated with presence of somatic TP53 mutations and that tumors from carriers of the Icelandic founder mutation in BRCA2, 999del5, had particularly complex chromosomal changes (Gretarsdottir et al, 1998;Eyfjord and Bodvarsdottir, 2005). We also reported an unexpectedly high proportion (15%) of cytogenetic abnormalities in histologically normal breast epithelium (Steinarsdottir et al, 2004). Prompted by these findings we have in the current study analyzed data from altogether 203 breast cancer patients with a follow-up period of 9-18 years and tested for associations between cytogenetic changes and various clinical, pathological, and genetic parameters as well as survival with the aim to shed some light on the biological and clinical significance of cytogenetic changes in nonmalignant breast tissue and breast cancer.…”

“…Culture methods were described in our previous publications (Steinarsdottir et al, 1995(Steinarsdottir et al, , 2004. Briefly, following overnight digestion in collagenase samples were cultured in Vitrogen-coated flasks (Nunc 25 cm 2 ) for 4-22 days.…”

“…Common numerical aberrations are gain of 7, 20, 18, and 8, and loss of X, 22, 13, and 17 (Teixeira, 2009). Chromosomal alterations have also been described in nonmalignant breast disease (Lundin and Mertens, 1998;Steinarsdottir et al, 2004). Many authors have studied specific chromosomal alterations and tried to correlate these with clinico-histopathological parameters and poor prognosis.…”

Gene expression abnormalities in histologically normal breast epithelium of breast cancer patients

“…Recently, abnormalities have been appreciated in histologically normal breast epithelium. These abnormalities include allelic imbalance or loss of heterozygosity, [1][2][3][4][5][6][7][8] aberrant methylation of p16 INK4 9 and of RASSF1A, 10 cytogenetic changes, 11,12 telomere shortening, 13 loss of IGF2 imprinting, 14 aberrant response to estrogen, 15 loss of RARb expression, 16 aberrant phosporylation of p38, 17 upregulation of EZH2. 18 Some of these abnormalities have been detected in normal-appearing tissue adjacent to the tumor, and others have been found at a distance from it.…”

“…The few studies comparing these groups have examined allelic imbalance, aneuploidy and methylation or expression of specific proteins, and have found abnormalities more frequently in patients with cancer than in controls. 7,8,10,12,[17][18][19] We hypothesized that by taking a comprehensive gene expression approach, we might detect consistent abnormalities in the normal-appearing epithelium of breast cancer patients, compared to controls. These abnormalities might suggest mechanisms predisposing to cancer, or activated early in carcinogenesis.…”