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

Abstract

Routinely used prognostic factors fail to predict clinical outcome in a significant proportion of breast cancer patients, implying that they can not detect some important biological characteristics. Chromosomal changes have been described in breast carcinomas for many years but their significance is not clear. We compared chromosomal changes with clinico-pathological characteristics and clinical outcome in 203 breast cancer patients with a follow-up of 9-18 years. Combining data from classical cytogenetics and flow cytometry revealed chromosomal abnormalities in 142 cases (70%). Of these, 51 (35.9%) contained two or more cytogenetically abnormal clones. Polyclonality was significantly associated with poor breast-cancer-specific survival (P = 0.03) within 5 years, independent of tumor size, lymph node metastases, and hormone receptors. Specific changes were similar to those previously described, but a new finding was a significant association between del 3p12p21 and poor survival. Polyclonality was significantly associated with TP53-mutations but not with a germline BRCA2 mutation. Less than one third of the polyclonal samples were identified by flow cytometry alone. Cytogenetic changes were detected in 17 out of 114 samples from non-tumorous tissue (15%), two of them identical with a clone in the corresponding tumor. Several samples contained clearly unrelated clones within the tumor and outside, implying either multifocal origin or early divergence. In conclusion, the common deletion on Chromosome 3p12p21 was associated with poor clinical outcome. Chromosomal polyclonality is common in breast carcinomas and predicts poor survival. Polyclonality was poorly detected by one-sample flow cytometry. Multiple sampling might improve the detection rate.

Molecular karyotyping and gene expression analysis in childhood cancer patients

“…Due to the chosen technique, only duplications and deletions are described in this study, while balanced structural changes remain undetected. Each patient displayed an almost unique pattern of aberrations which is consistent with the idea of the multi-causation of cancer and findings of spontaneous abnormalities in normal human fibroblasts from patients with Li-Fraumeni cancer syndrome [39] and chromosomal changes in non-cancerous breast tissue for breast carcinoma patients [40]. Interestingly, an abnormal gene expression in fibroblasts was detected in patients with Gorlin syndrome (GS), which is a hereditary disorder with tumorigenicity, caused by constitutive hyperactivity of hedgehog signaling.…”

Correlation of morphological markers of chromosomal instability in fine needle aspiration cytology with grade of breast cancer

“…Studies of breast cancer karyotypes have demonstrated that this type of cancer frequently has the structural genomic aberrations as seen in other forms of human cancer, including aneuploidy. [4][5][6][7] Furthermore, several previous studies have shown variability of chromosome numbers from cell to cell within a given breast cancer, [8][9][10][11] suggesting that breast cancers also have chromosomal instability.…”