Affiliations of authors: F. R. Miller, L. Tait, Breast Cancer Program, Barbara Ann Karmanos Cancer Institute, Detroit, MI, and Department of Pathology, Wayne State University School of Medicine, Detroit, MI; S. J. Santner, Breast Cancer Program, Barbara Ann Karmanos Cancer Institute, and Department of Medicine, Wayne State University; P. J. Dawson, Department of Pathology, James A. Haley Veterans Hospital, Tampa, FL, and Department of Pathology, University of South Florida, Tampa, FL.
Correspondence to: Fred R. Miller, Ph.D., Barbara Ann Karmanos Cancer Institute, 110 E. Warren Ave., Detroit, MI 48201 (e-mail: millerf{at}karmanos.org).
Ductal carcinoma in situ (DCIS) is becoming increasingly common, accounting for 25%30% of newly diagnosed cases of breast cancer (1). The comedo type represents about 40% of the cases and carries the worst prognosis (2). The subsequent incidence of recurrence in patients presenting previously with comedo DCIS was 20% compared with 5% for noncomedo DCIS in one study (3). National Surgical Adjuvant Breast and Bowel Project Protocol B-17 reported a 40% incidence of ipsilateral breast cancer after lumpectomy of comedo DCIS and found that comedo necrosis is the only important predictor for recurrence after lumpectomy (4).
A recurring theme in the National Institutes of Health Breast Cancer Progress Review Group report (http://osp.nci.nih.gov/PRGReports/BPRGReport/bprgtableofcontents.htm) is the need for xenograft models of early human breast disease such as DCIS. The MCF10 model includes normal immortalized breast epithelial cells (MCF10A), premalignant variants (MCF10AT lines) that form simple ducts in xenografts, and malignant variants (MCF10CA lines) (57).
The clonal cell line MCF10DCIS. com was cloned from a cell culture initiated from a xenograft lesion obtained after two successive trocar passages of a lesion formed by premalignant MCF10AT cells. Injection of MCF10DCIS.com within 22 passages resulted in rapidly growing lesions that are predominantly comedo DCIS. The tumor mass is composed of tightly packed tubular structures, many with central necrosis (Fig. 1). Silver staining reveals distinct intact basement membranes surrounding each ductular structure and emphasizes the necrotic centers (Fig. 1
, A). The central necrosis is coagulative and often infiltrated with neutrophils. Mitotic figures are frequent and epithelial cells have moderate amounts of foamy cytoplasm (Fig. 1
, B). The nuclei are large and vesicular with large nucleoli. In some areas, the cytoplasm is clear and the cell boundaries are well defined. A distinct myoepithelial layer exists along the basement membrane. A desmoplastic response is evident around some ducts. Although early (3-week) lesions are predominantly DCIS, invasive areas develop and may account for half of the older (9-week) lesions. Further evidence of the progressive potential of the line is that late-passage cells (passage 37) have a more extensive invasive component.
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In summary, we have obtained a human cell line that forms DCIS when xenografted into immunodeficient mice. This property should render it very useful for the testing of chemopreventive agents, for the screening of cancer-causing agents, and for genetic analyses. The fact that this cell line is a member of the MCF10 panel of cell lines, derived from a single patient, representing sequential stages of progression as shown by xenograft lesion formed, makes it all the more valuable for the analysis of genetic progression in human breast disease.
REFERENCES
1 Schwartz GF, Solin LJ, Olivotto IA, Ernster VL, Pressman PI. Consensus Conference on the Treatment of In Situ Ductal Carcinoma of the Breast, April 2225, 1999. Cancer 2000;88:94654.[Medline]
2 Silverstein MJ, Lagios MD, Craig PH, Waisman JR, Lewinsky BS, Colburn WJ, et al. A prognostic index for ductal carcinoma in situ of the breast. Cancer 1996;77:226774.[Medline]
3 Solin LJ, Yeh IT, Kurtz J, Fourquet A, Recht A, Kuske R, et al. Ductal carcinoma in situ (intraductal carcinoma) of the breast treated with breast-conserving surgery and definitive irradiation. Correlation of pathologic parameters with outcome of treatment. Cancer 1993;71:253242.[Medline]
4 Fisher ER, Dignam J, Tan-Chiu E, Costantino J, Fisher B, Paik S, et al. Pathologic findings from the National Surgical Adjuvant Breast Project (NSABP) eight-year update of Protocol B-17: intraductal carcinoma. Cancer 1999;86:42938.[Medline]
5 Dawson PJ, Wolman SR, Tait L, Heppner GH, Miller FR. MCF10AT: a model for the evolution of cancer from proliferative breast disease. Am J Pathol 1996;148:3139.[Abstract]
6 Miller FR, Soule HD, Tait L, Pauley RJ, Wolman SR, Dawson PJ, et al. Xenograft model of progressive human proliferative breast disease. J Natl Cancer Inst 1993;85:172532.[Abstract]
7 Santner SJ, Miller F, Dawson P, Tait L, Soule H, Eliason J, et al. MCF-10CA1 cell lines: new highly tumorigenic derivatives of the MCF-10AT system [abstract]. Proc Am Assoc Cancer Res 1998;39:2023.
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