Classification of ductal carcinoma in situ by gene expression profiling.
BACKGROUND
Ductal carcinoma in situ (DCIS) is characterised by the intraductal proliferation of malignant epithelial cells. Several histological classification systems have been developed, but assessing the histological type/grade of DCIS lesions is still challenging, making treatment decisions based on these features difficult. To obtain insight in the molecular basis of the development of different types of DCIS and its progression to invasive breast cancer, we have studied differences in gene expression between different types of DCIS and between DCIS and invasive breast carcinomas.


METHODS
Gene expression profiling using microarray analysis has been performed on 40 in situ and 40 invasive breast cancer cases.


RESULTS
DCIS cases were classified as well- (n = 6), intermediately (n = 18), and poorly (n = 14) differentiated type. Of the 40 invasive breast cancer samples, five samples were grade I, 11 samples were grade II, and 24 samples were grade III. Using two-dimensional hierarchical clustering, the basal-like type, ERB-B2 type, and the luminal-type tumours originally described for invasive breast cancer could also be identified in DCIS.


CONCLUSIONS
Using supervised classification, we identified a gene expression classifier of 35 genes, which differed between DCIS and invasive breast cancer; a classifier of 43 genes could be identified separating between well- and poorly differentiated DCIS samples.
Hannemann
Juliane
J
Division of Experimental Therapy, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Velds
Arno
A
Halfwerk
Johannes B G
JB
Kreike
Bas
B
Peterse
Johannes L
JL
van de Vijver
Marc J
MJ
D001943:Breast Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000145:classification / Q000235:genetics* / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000145:classification / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans