M. Aubele et al., Extensive ductal carcinoma in situ with small foci of invasive ductal carcinoma: Evidence of genetic resemblance by CGH, INT J CANC, 85(1), 2000, pp. 82-86
Although ductal carcinoma in site (DCIS) of the breast is accepted as a pot
ential precursor lesion for invasive ductal cancer (IDC), the critical gene
tic events associated with the tumor progression remain unknown. Since some
extensive DCIS may show a small focus of IDC, these cases seem to be parti
cularly suitable to investigate the primary abnormalities that determine th
e progression from in situ to early invasive cancer. We combined laser-micr
odissection with degenerative oligonucleotide-primed PCR (DOP-PCR) and comp
arative genomic hybridization (CGH) to detect copy number changes in 7 case
s of extensive (>4 cm) DCIS with I small adjacent invasive focus. In 3 of t
he cases, single lymph node metastases (LN) were already present and were a
lso investigated. Analysis of DCIS, IDC and LN components in the same patie
nts revealed several consistent chromosomal changes present at all 3 sites:
Iq, 7q, 8q, 16, 17, 19, 20q, 21q and 22q, the most frequent losses on 4q,
11q and 13q. DNA gain on 3p and 12q were more frequently found in IDC than
in DCIS, suggesting the presence of proto-oncogenes activated during the pr
ogression to invasive cancer on these regions. Using paired analysis, resem
blence of alterations found in DCIS and IDC could be quantified (odds ratio
7.0, p less than or equal to 0.01). Gains on 6p, 10q, 14q and 15q and loss
es on 9p were identified in DCIS and IDC but not in LN, which may, therefor
e, represent early events in the carcinogenic process. Additional losses we
re found in the LNs on 2q, 3q, 5q, 6q, 12q and 16q. CGH results on chromoso
me I and 20 were confirmed by FISH and on chromosomal region 9p by microsat
ellite analyses. Our findings strongly underline the precursor status of hi
gh-grade DCIS, in which most of the chromosomal changes identified in IDC a
re already present. However, although the early stages of breast cancer, i.
e., DCIS and the small foci of IDC were mainly characterized by DNA gains,
the progression to metastatic tumor (LN) must have involved additional DNA
losses on several regions. (C) 2000 Wiley-Liss, Inc.