title: Characterisation of breast fine-needle aspiration biopsies by centrosome aberrations and genomic instability.
abstract: Recent studies have suggested that aneuploidy in malignant tumours could be a consequence of centrosome aberrations. Using immunofluorescence analysis with an antibody against gamma-tubulin and DNA image cytometry, we measured centrosome aberrations and DNA ploidy patterns in fine-needle aspiration biopsies (FNABs) of 58 breast lesions. Benign lesions did not show any centrosome aberrations. DNA diploid carcinomas showed a mean percentage of cells with centrosomal defects of 2.1%. The aneuploid invasive carcinomas could be divided into two subgroups by their significantly (P=0.0003) different percentage of cells with centrosome aberrations (2.0 and 10.3%, respectively) and their significantly (P=0.0003) different percentage of cells with nonmodal DNA content values determined by the Stemline Scatter Index (SSI), a measure of genomic instability. The percentage of cells with centrosome aberrations demonstrated a positive, linear correlation with the corresponding SSI (r=0.82, P<0.0001) and loss of tissue differentiation (r=0.78, P<0.0001). Our results indicate the percentage of cells with centrosome aberrations as being sufficient to divide the investigated tumours into three significantly different groups: benign lesions with no centrosomal aberrations, and two malignant tumour types with mean values of 2.1 and 9.6% of centrosomal defects, respectively. Together, these results demonstrate that centrosome aberrations correlate with genomic instability and loss of tissue differentiation. Furthermore, this study shows the feasibility of centrosomal analysis in FNAB of the breast and suggests centrosomal aberrations as possessing diagnostic and prognostic value.
authors.affiliation: Department of Oncology and Pathology, Division of Cellular and Molecular Analysis, Cancer Center Karolinska (CCK), R8:04, Karolinska Institute and Hospital, 17176 Stockholm, Sweden. Ulrike.Kronenwett@cck.ki.se
authors.forename: U
authors.initials: U
authors.lastname: Kronenwett
authors.forename: S
authors.initials: S
authors.lastname: Huwendiek
authors.forename: J
authors.initials: J
authors.lastname: Castro
authors.forename: T
authors.initials: T
authors.lastname: Ried
authors.forename: G
authors.initials: G
authors.lastname: Auer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D044963:Biopsy, Fine-Needle; D001943:Breast Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology*; D018385:Centrosome / Q000473:pathology*; D004273:DNA, Neoplasm / Q000032:analysis*; D005455:Fluorescent Antibody Technique; D042822:Genomic Instability; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008875:Middle Aged
chemical_list: D004273:DNA, Neoplasm