Cytogenetic polyclonality of breast carcinomas: association with clinico-pathological characteristics and outcome.

• Published in: Genes, Chromosomes and Cancer
• Main Authors: Steinarsdottir, Margret, Gudmundsson, Ingi Hrafn, Jonasson, Jon Gunnlaugur, Olafsdottir, Elinborg J, Eyfjörd, Jorunn E, Ogmundsdottir, Helga M
• Other Authors: Chromosome Laboratory, Department of Genetics and Molecular Medicine, Landspitali University Hospital, Reykjavík, Iceland.
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley-Liss 2012
• Subjects: Adult; Aged; 80 and over; BRCA2 Protein; Breast Neoplasms; Chi-Square Distribution; Chromosome Aberrations; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Karyotyping; Middle Aged; Multivariate Analysis; Risk Factors; Tumor Suppressor Protein p53; Meier; Iceland
• Online Access: http://hdl.handle.net/2336/226845; https://doi.org/10.1002/gcc.20915

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field. 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. Icelandic Cancer Society Landspitali Science Fund University of Iceland