Classification of ductal carcinoma in situ by gene expression profiling - PubMed (original) (raw)

Classification of ductal carcinoma in situ by gene expression profiling

Juliane Hannemann et al. Breast Cancer Res. 2006.

Abstract

Introduction: 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.

Conclusion: 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.

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Figures

Figure 1

Figure 1

Unsupervised hierarchical clustering of in situ and invasive samples. (a) Dendrogram of all in situ (n = 40) and all invasive (n = 40) samples. (b) Scaled-down representation of the entire cluster shown in (a) (1,706 genes). (c) Dendogram of poorly differentiated ductal carcinoma in situ (n = 14) and grade 3 invasive (n = 24) samples. (d) Entire cluster of (c) (1,119 genes). Yellow indicates in situ samples, and blue indicates invasive samples. i, intermediately differentiated; IHC, immunohistochemistry; i/p, intermediately/poorly differentiated; LCIS, lobular carcinoma in situ; p, poorly differentiated; w, well differentiated; w/i, well/intermediately differentiated.

Figure 2

Figure 2

Euclidean distance and heatmaps of the in situ and invasive samples using the classifiers obtained after cross-validation. (a) All ductal carcinoma in situ (DCIS) (n = 40) and all invasive (n = 40) samples. The classifiers consist of 80 genes. (b) Poorly differentiated DCIS (n = 14) versus invasive grade 3 samples (n = 24) using a classifier of 35 genes. p, poorly differentiated.

Figure 3

Figure 3

Correlation plots and heatmaps of the in situ samples using the classifiers obtained after cross-validation. (a) Well- (n = 6) versus poorly (n = 14) differentiated ductal carcinoma in situ (DCIS). The classifiers consist of 43 genes. (b) Well-/well-intermediately (n = 16) versus intermediately-poorly/poorly (n = 20) differentiated DCIS using a classifier of 78 genes. i-p, intermediately-poorly differentiated; p, poorly differentiated; w, well differentiated; w-i, well-intermediately differentiated.

Figure 4

Figure 4

Unsupervised hierarchical clustering of the in situ samples. (a) Dendrogram of all 40 in situ samples. (b) Scaled-down representation of the entire cluster of (a) (5,788 genes). (c) Dendrogram of only the well- (n = 6) and poorly (n = 14) differentiated ductal carcinoma in situ (DCIS) cases. (d) Entire cluster of (c) (4,493 genes). Yellow indicates well-differentiated DCIS, brown indicates poorly differentiated DCIS, black indicates DCIS samples with an intermediately differentiated component, and gray indicates special cases. i, intermediately differentiated; IHC, immunohistochemistry; i-p, intermediately-poorly differentiated; LCIS, lobular carcinoma in situ; p, poorly differentiated; w, well differentiated; w-i, well-intermediately differentiated.

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