Molecular diversity in ductal carcinoma in situ (DCIS) and early invasive breast cancer

Aslaug Aamodt Muggerud, Michael Hallett, Hilde Johnsen, Kristine Kleivi, Wenjing Zhou, Simin Tahmasebpoor, Rose-Marie Amini, Johan Botling, Anne-Lise Børresen-Dale, Therese Sørlie, Fredrik Wärnberg

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Abstract

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.
Original languageEnglish
Pages (from-to)357-368
JournalMolecular Oncology
Volume4
Issue number4
DOIs
Publication statusPublished - 2010
MoE publication typeA1 Journal article-refereed

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Carcinoma, Intraductal, Noninfiltrating
Breast Neoplasms
Ductal Carcinoma
Gene Expression
Neoplasms
Human Genome
Transcriptome
Genes
Cluster Analysis
Breast
Logistic Models

Keywords

  • DCIS
  • Molecular subtypes of breast cancer
  • Progression
  • Gene expression

Cite this

Muggerud, A. A., Hallett, M., Johnsen, H., Kleivi, K., Zhou, W., Tahmasebpoor, S., ... Wärnberg, F. (2010). Molecular diversity in ductal carcinoma in situ (DCIS) and early invasive breast cancer. Molecular Oncology, 4(4), 357-368. https://doi.org/10.1016/j.molonc.2010.06.007
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. / Molecular diversity in ductal carcinoma in situ (DCIS) and early invasive breast cancer. In: Molecular Oncology. 2010 ; Vol. 4, No. 4. pp. 357-368.
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Muggerud, AA, Hallett, M, Johnsen, H, Kleivi, K, Zhou, W, Tahmasebpoor, S, Amini, R-M, Botling, J, Børresen-Dale, A-L, Sørlie, T & Wärnberg, F 2010, 'Molecular diversity in ductal carcinoma in situ (DCIS) and early invasive breast cancer', Molecular Oncology, vol. 4, no. 4, pp. 357-368. https://doi.org/10.1016/j.molonc.2010.06.007

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 journalArticleScientificpeer-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

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SP - 357

EP - 368

JO - Molecular Oncology

JF - Molecular Oncology

SN - 1574-7891

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