Comparative genomic hybridization of ductal carcinomain situ of the breast?evidence of multiple genetic pathways

Abstract

There is strong evidence that ductal carcinoma in situ (DCIS) represents a precursor lesion of invasive breast cancer. In order to analyse specific chromosomal alterations of DCIS, 38 paraffin‐embedded specimens of DCIS and six associated invasive carcinomas were examined by means of comparative genomic hybridization (CGH). Losses of 16q material were seen almost exclusively in well‐ and intermediately‐differentiated DCIS. These two subgroups differed in the average number of genetic imbalances, 2·5 and 5·5 respectively. Additionally, a higher frequency of gains of 1q and losses of 11q material was seen in intermediately‐differentiated in contrast to well‐differentiated DCIS. Poorly‐differentiated DCIS displayed a higher frequency of amplifications (17q12, 11q13) and a higher average rate of genetic imbalances (7·1). Analysis of adjacent invasive breast carcinoma revealed a genetic pattern almost identical to the one seen in the DCIS counterpart. These data characterize DCIS as a genetically far‐advanced, heterogeneous lesion and as a direct precursor of invasive breast cancer. Copyright © 1999 John Wiley & Sons, Ltd.

Evaluation of pathways for progression of heterogeneous breast tumors

“…Their conclusion was confirmed with microsatellite markers (Roylance et al, 2002). However, based on comparative genomic hybridization, Buerger et al (1999) proposed that atypical hyperplasia could progress to all three grades of DCIS and, in addition, that there could be progression between grades of DCIS. The nonlinear and branched pathways take into account each of these possibilities.…”

“…It is important to able to predict how a tumor will progress, since this may influence treatment decisions. Several pathways describing the relationship between grades of DCIS and grades of IDC have been proposed (Buerger et al, 1999;Gupta et al, 1997;Leong et al, 2001;Mommers et al, 2001b;Roylance et al, 1999Roylance et al, , 2002. However, it is not clear which pathway best describes the biological relationship between grades of DCIS and IDC.…”

Tumour markers in breast carcinoma correlate with grade rather than with invasiveness

“…Several studies have indicated that poorly differentiated DCIS might be a precursor to poorly differentiated invasive breast cancer and well-differentiated DCIS to well-differentiated invasive breast cancer. Both histopathological grade and DNA contents have been reported to be similar in the invasive and in the in situ parts of mixed breast carcinomas (Iglehart et al, 1995;Douglas-Jones et al, 1996;Gupta et al, 1997;Buerger et al, 1999).…”

Genetic variation in five genes important in telomere biology and risk for breast cancer

“…Breast cancer fits the paradigm of dysfunctional telomere-induced genomic instability, because the transition of breast duct hyperplasia to ductal carcinoma in situ likely results from a period of telomere crisis (DePinho, 2000;Chin et al, 2004). As breast cancer progresses further to invasive and metastatic stages, telomere dysfunction and genomic instability become more apparent (Nishizaki et al, 1997;Buerger et al, 1999;Chin et al, 2004). As cells progress through the latter stages of carcinogenesis, telomeres become relatively stable.…”