Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 357-368 |
| Journal | Molecular Oncology |
| Volume | 4 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2010 |
| MoE publication type | A1 Journal article-refereed |
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Keywords
- DCIS
- Molecular subtypes of breast cancer
- Progression
- Gene expression
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Molecular diversity in ductal carcinoma in situ (DCIS) and early invasive breast cancer. / Muggerud, Aslaug Aamodt; Hallett, Michael; Johnsen, Hilde; Kleivi, Kristine; Zhou, Wenjing; Tahmasebpoor, Simin; Amini, Rose-Marie; Botling, Johan; Børresen-Dale, Anne-Lise; Sørlie, Therese; Wärnberg, Fredrik.
In: Molecular Oncology, Vol. 4, No. 4, 2010, p. 357-368.Research output: Contribution to journal › Article › Scientific › peer-review
TY - JOUR
T1 - Molecular diversity in ductal carcinoma in situ (DCIS) and early invasive breast cancer
AU - Muggerud, Aslaug Aamodt
AU - Hallett, Michael
AU - Johnsen, Hilde
AU - Kleivi, Kristine
AU - Zhou, Wenjing
AU - Tahmasebpoor, Simin
AU - Amini, Rose-Marie
AU - Botling, Johan
AU - Børresen-Dale, Anne-Lise
AU - Sørlie, Therese
AU - Wärnberg, Fredrik
PY - 2010
Y1 - 2010
N2 - Ductal carcinoma in situ (DCIS) is a non‐invasive form of breast cancer where cells restricted to the ducts exhibit an atypical phenotype. Some DCIS lesions are believed to rapidly transit to invasive ductal carcinomas (IDCs), while others remain unchanged. Existing classification systems for DCIS fail to identify those lesions that transit to IDC. We studied gene expression patterns of 31 pure DCIS, 36 pure invasive cancers and 42 cases of mixed diagnosis (invasive cancer with an in situ component) using Agilent Whole Human Genome Oligo Microarrays 44k. Six normal breast tissue samples were also included as controls. qRT‐PCR was used for validation. All DCIS and invasive samples could be classified into the “intrinsic” molecular subtypes defined for invasive breast cancer. Hierarchical clustering establishes that samples group by intrinsic subtype, and not by diagnosis. We observed heterogeneity in the transcriptomes among DCIS of high histological grade and identified a distinct subgroup containing seven of the 31 DCIS samples with gene expression characteristics more similar to advanced tumours. A set of genes independent of grade, ER‐status and HER2‐status was identified by logistic regression that univariately classified a sample as belonging to this distinct DCIS subgroup. qRT‐PCR of single markers clearly separated this DCIS subgroup from the other DCIS, and contains samples from several histopathological and intrinsic molecular subtypes. The genes that differentiate between these two types of DCIS suggest several processes related to the re‐organisation of the microenvironment. This raises interesting possibilities for identification of DCIS lesions both with and without invasive characteristics, which potentially could be used in clinical assessment of a woman's risk of progression, and lead to improved management that would avoid the current over‐ and under‐treatment of patients.
AB - Ductal carcinoma in situ (DCIS) is a non‐invasive form of breast cancer where cells restricted to the ducts exhibit an atypical phenotype. Some DCIS lesions are believed to rapidly transit to invasive ductal carcinomas (IDCs), while others remain unchanged. Existing classification systems for DCIS fail to identify those lesions that transit to IDC. We studied gene expression patterns of 31 pure DCIS, 36 pure invasive cancers and 42 cases of mixed diagnosis (invasive cancer with an in situ component) using Agilent Whole Human Genome Oligo Microarrays 44k. Six normal breast tissue samples were also included as controls. qRT‐PCR was used for validation. All DCIS and invasive samples could be classified into the “intrinsic” molecular subtypes defined for invasive breast cancer. Hierarchical clustering establishes that samples group by intrinsic subtype, and not by diagnosis. We observed heterogeneity in the transcriptomes among DCIS of high histological grade and identified a distinct subgroup containing seven of the 31 DCIS samples with gene expression characteristics more similar to advanced tumours. A set of genes independent of grade, ER‐status and HER2‐status was identified by logistic regression that univariately classified a sample as belonging to this distinct DCIS subgroup. qRT‐PCR of single markers clearly separated this DCIS subgroup from the other DCIS, and contains samples from several histopathological and intrinsic molecular subtypes. The genes that differentiate between these two types of DCIS suggest several processes related to the re‐organisation of the microenvironment. This raises interesting possibilities for identification of DCIS lesions both with and without invasive characteristics, which potentially could be used in clinical assessment of a woman's risk of progression, and lead to improved management that would avoid the current over‐ and under‐treatment of patients.
KW - DCIS
KW - Molecular subtypes of breast cancer
KW - Progression
KW - Gene expression
U2 - 10.1016/j.molonc.2010.06.007
DO - 10.1016/j.molonc.2010.06.007
M3 - Article
VL - 4
SP - 357
EP - 368
JO - Molecular Oncology
JF - Molecular Oncology
SN - 1574-7891
IS - 4
ER -