MCF10DCIS.com xenograft model of human comedo ductal carcinoma in situ.

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) (5–7). 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