Background: The ductal carcinoma in situ (DCIS) of the
mammary gland represents an early, pre-invasive stage in the
development of invasive breast carcinoma. Since DCIS is a curable
disease, it would be highly desirable to identify molecular markers
that allow early detection. Mice transgenic for the WAP-SV40 early
genome region were used as a model for DCIS development. Gene
expression profiling was carried out on DCIS-bearing mice and
control animals. Additionally, a set of human DCIS and invasive
mammary tumors were analyzed in a similar fashion. Enhanced
expression of these marker genes in human and murine samples was
validated by quantitative RT-PCR. Besides, marker gene expression
was also validated by immunohistochemistry of human samples.
Furthermore in silico analyses using an online microarray database
were performed. Results: In DCIS-mice seven genes were identified
that were significantly up-regulated in DCIS: DEPDC1, NUSAP1,
EXO1, RRM2, FOXM1, MUC1 and SPP1. A similar up-regulation
of homologues of the murine genes was observed in human DCIS
samples. Enhanced expression of these genes in DCIS and IDC
(invasive ductal carcinoma) was validated by quantitative RT-PCR
and immunohistochemistry. Conclusions: By comparing murine
markers for the ductal carcinoma in situ (DCIS) of the mammary
gland with genes up-regulated in human DCIS-samples we were
able to identify a set of genes which might allow early detection of
DCIS and invasive carcinomas in the future. The similarities
between gene expression in DCIS and invasive carcinomas in our
data suggest that the early detection and treatment of DCIS is of
utmost relevance for the survival of patients who are at high risk of
developing breast carcinomas
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