Differences in genetic alterations between primary lobular and ductal breast cancers detected by comparative genomic hybridization

Abstract

Infiltrating ductal (DC) and lobular carcinoma (LC) of the breast represent the most frequently observed varieties of invasive breast cancer, characterized by differences in their histological and clinical properties. Although comparative genomic hybridization (CGH) of invasive breast carcinomas has revealed a complex and consistent pattern of DNA copy number changes, the data with regard to type specific aberrations are limited. A comprehensive study was therefore performed on 19 LCs and 29 DCs to ascertain type-specific differences of unbalanced DNA copy number changes by CGH. Statistical analysis revealed significantly higher frequencies for underrepresentation of chromosomes 16q (p<0.01), 22 (p<0.05), and 17q (p<0.05), and a lower frequency for overrepresentation of chromosome 8q (p<0.01) in LC. Similar frequencies of non-random chromosomal changes in LC and DC were obtained for gain of 1q (74%/59%) and loss of 19p (53%/52%), parts of 1p (42%/41%) and 11q (21%/24%). Less frequently, gains mainly involving parts of chromosomes 20q, 20p, 3q, and 5p and partial losses of chromosomes 17p and 13 were observed in both groups of tumours. Minimal regions of overlapping amplifications were mapped to 17q23 exclusively in DC (17%) and 11q13-q14 in both DC and LC (21% and 11%, respectively). High occurrences of DNA copy number decreases were detected at the distal part of chromosomes 1p, 19 and 22, but further analysis is required to confirm these imbalances. It is suggested that the observed differences are involved in the development of type-specific properties of DC and LC.

8p deletion is strongly linked to poor prognosis in breast cancer

“…The higher rate of 8p deletions in NST as compared to lobular cancer is not surprising as most genomic alterations are more frequent in NST than in lobular carcinomas such as amplifications of HER2, 41,49 MYC, 41 MDM1, 41 and AIB1, 50 or overexpression of p53. 51 A higher rate of 8p deletions in NST than in lobular carcinomas has earlier been suggested by data from Guenther et al 52 finding loss of 8p in 28% of NST but only in 5% of lobular carcinomas (p D 0.05) and by Thor et al 53 reporting 8p in 33% of NST but only in 13% of lobular carcinomas (p D 0.12). Given the general link of 8p deletions with unfavorable disease outcome, the high rate of 8p deletions in papillary cancer and cancers with medullary features was unexpected.…”

Loss of expression of chromosome 16q genes DPEP1 and CTCF in lobular carcinoma in situ of the breast

“…In a recent study, we have proposed the existence of a family of low grade breast carcinoma, suggesting a developmental pathway from normal to precursor to breast carcinoma [3]. We and others [4][5][6][7] have confirmed a high association between LCIS and the development of ILC. Therefore, its detection and treatment substantially improves survival [1].…”

“…16q loss is seen with a similar high frequency in LCIS, ILC, tubular cancer, and in low and intermediate DCIS, whereas high grade invasive or in situ ductal carcinomas shows 16q loss much less frequently [4,5,9]. The loss of 16q regions is believed to be an early genetic event in the development of invasive breast cancer from in situ lesions [6].…”

Invasive lobular carcinoma: to grade or not to grade

“…Our results suggest that HER2/neu gene amplification is of minor importance in the development or progression of invasive lobular carcinoma regardless of grade, in contrast with invasive ductal carcinomas. Molecular characterization of invasive lobular carcinomas has shown that they have a higher incidence of loss of chromosome 17q than ductal carcinomas (P ¼ 0.3) and that ductal tumors have a higher incidence of 17q22-24 amplification than their lobular counterparts, 54 factors that may influence HER2/neu gene copy number and hence protein expression. A cDNA microarray study similarly showed that only two of 17 lobular carcinomas arrayed displayed HER2/neu gene overexpression.…”