Analysis of stromal signatures in the tumor microenvironment of ductal carcinoma in situ

• Published in: Breast cancer research and treatment 2010-09, Vol.123 (2), p.397-404
• Main Authors: Sharma, M, Beck, A. H, Webster, J. A, Espinosa, I, Montgomery, K, Varma, S, van de Rijn, M, Jensen, K. C, West, R. B
• Format: Article
• Language: English
• Subjects: Analysis; Biological and medical sciences; Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; Breast cancer; Breast Neoplasms - chemistry; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cancer research; Cancer stroma; Cancer therapies; Carcinoma, Ductal; Carcinoma, Ductal, Breast - chemistry; Carcinoma, Ductal, Breast - genetics; Carcinoma, Ductal, Breast - pathology; Carcinoma, Intraductal, Noninfiltrating - chemistry; Carcinoma, Intraductal, Noninfiltrating - genetics; Carcinoma, Intraductal, Noninfiltrating - pathology; Disease Progression; Ductal carcinoma in situ; Female; fibroblasts; Fibroblasts - chemistry; Gene expression; Gene Expression Profiling - methods; Gene Expression Regulation, Neoplastic; Genes; Genotype; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; Macrophage; Macrophages - chemistry; Mammary gland diseases; Medical sciences; Medicine; Medicine & Public Health; Neoplasm Invasiveness; Neoplasm Staging; Oligonucleotide Array Sequence Analysis; Oncology; Phenotype; Preclinical Study; Stromal Cells - chemistry; Stromal Cells - pathology; Tissue Array Analysis; Tumor microenvironment; Tumors
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-009-0654-0

Recent advances in the study of the tumor microenvironment have revealed significant interaction between tumor cells and their surrounding stroma in model systems. We have previously shown that two distinct stromal signatures derived from a macrophage (CSF1) response and a fibroblastic (DTF-like) response are present in subsets of invasive breast cancers and show a correlation with clinical outcome [1-3]. In the present study we explore whether these signatures also exist in the stroma of ductal carcinoma in situ (DCIS). We studied the signatures by both gene expression profile analysis of a publically available data set of DCIS and by immunohistochemistry (IHC) on a tissue microarray of DCIS and invasive breast cancer cases. Both the gene expression and immunohistochemical data show that the macrophage response and fibroblast expression signatures are present in the stroma of subsets of DCIS cases. The incidence of the stromal signatures in DCIS is similar to the incidence in invasive breast cancer that we have previously reported. We also find that the macrophage response signature is associated with higher grade DCIS and cases which are ER and PR negative, whereas the fibroblast signature was not associated with any clinicopathologic features in DCIS. A comparison of 115 matched cases of DCIS and invasive breast cancer found a correlation between the type of stromal response in DCIS and invasive ductal carcinoma (IDC) within the same patient for both the macrophage response and the fibroblast stromal signatures (P = 0.03 and 0.08, respectively). This study is a first characterization of these signatures in DCIS. These signatures have significant clinicopathologic associations and tend to be conserved as the tumor progresses from DCIS to invasive breast cancer.