Ductal carcinoma in situ: A review of recent advances
This review summarizes recent findings on ductal carcinoma in situ of the breast and their impact on prognosis and management of the disease.
Great advances have been made in our understanding of ductal carcinoma in situ. Nuclear grading is probably the most important pathological factor that affects clinical outcome and correlates with distinct genetic pathways. Identifying key molecules in each pathway may provide better markers for prognostic, predictive and therapeutic purposes. Not all cases of ductal carcinoma in situ will progress to invasive ductal carcinoma, and identifying this subgroup of patients should lead to a reduction of overtreatment. Progenitor cell theory at the cellular level and sick lobe theory at the architectural level may help provide a better understanding of ductal carcinoma in situ from a different perspective and facilitate the development of individualized therapy. Prevention of local recurrence is the primary goal for treatment. Debate continues, however, on the use of radiotherapy, hormonal therapy, and sentinel lymph node biopsy. A panel of molecular markers may be needed for accurately predicting clinical outcome for the disease.
Understanding the carcinogenesis of ductal carcinoma in situ at the molecular level may lead to an optimal individualized therapy with minimal over or undertreatment.
Available from: PubMed Central
- "Ductal Carcinoma in situ (DCIS) is the term given to those cancers which demonstrate marked atypia, but are non-invasive. While DCIS without associated invasive breast cancer (IBC) is rarely detected as a palpable lump, it is estimated to account for approximately 20–30% of those cancers found in mammography screening programs , . It can be expected that as mammography screening in developing countries becomes more common, so too will the diagnosis of DCIS. "
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ABSTRACT: As the field of molecular imaging evolves and increasingly is asked to fill the discovery and validation space between basic science and clinical applications, careful consideration should be given to the models in which studies are conducted. The MIN-O mouse model series is an established in vivo model of human mammary precancer ductal carcinoma in situ with progression to invasive carcinoma. This series of transplant lines is propagated in vivo and experiments utilizing this model can be completed in non-engineered immune intact FVB/n wild type mice thereby modeling the tumor microenvironment with biological relevance superior to traditional tumor cell xenografts. Unfortunately, the same qualities that make this and many other transplant lines more biologically relevant than standard cell lines for molecular imaging studies present a significant obstacle as somatic genetic re-engineering modifications common to many imaging applications can be technically challenging. Here, we describe a protocol for the efficient lentiviral transduction of cell slurries derived from precancerous MIN-O lesions, in vitro culture of "MIN-O-spheres" derived from single cell clones, and the subsequent transplantation of these spheres to produce transduced sublines suitable for optical imaging applications. These lines retain the physiologic and pathologic properties, including multilineage differentiation, and complex microanatomic interaction with the host stroma characteristic of the MIN-O model. We also present the in vivo imaging and immunohistochemical analysis of serial transplantation of one such subline and detail the progressive multifocal loss of the transgene in successive generations.
Available from: Jeong S Han
- "The identification of markers that can predict recurrence and/or invasion in DCIS is critical. Some studies have showed that expression of ER, PR, HER2, Ki67, and p53 correlate with tumor grade rather than invasion     . "
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ABSTRACT: There is a paucity of data regarding molecular subtypes of pure ductal carcinoma in situ (pDCIS). We evaluated the expression of ER, PR, HER2, Ki67, and p53 and DNA ploidy in 118 pDCIS and 100 invasive breast carcinomas (IBCAs) by routine IHC and classified them according to molecular subtypes. Quantification of biomarkers and DNA ploidy was performed by image analysis. Expression of ER, PR, and high ki67 was more frequent in pDCIS compared to IBCA. High-grade tumors had lower ER and PR expression, high Ki67, overexpression of HER2 and p53, and DNA aneuploidy. Luminal A and HER2 subtypes were more common in pDCIS, and triple negative was more prevalent in IBCA. In both groups, HER2 and triple negative subtypes were characterized by high ki67, overexpression of p53, and DNA aneuploidy compared to luminal subtypes. Molecular subtypes of IBCA are distinct from those of pDCIS. Invasion is characterized by change in phenotype in some tumors.
Available from: Mutsuko Yamamoto-Ibusuki
- "Since the introduction of mammography in breast cancer screening, increasing numbers of DCIS are now being identified . About 10 years ago, DCIS accounted for only 1–5% of all newly diagnosed cases of breast cancer, whereas the frequency has increased recently to 15–20% [3,4]. According to the criteria of the American Joint Committee on Cancer (AJCC), IDC with a microscopic focus of invasion less than or equal to 0.1 cm in the longest dimension, is defined as T1mic . "
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ABSTRACT: Widespread use of mammography in breast cancer screening has led to the identification of increasing numbers of patients with ductal carcinoma in situ (DCIS). DCIS of the breast with an area of focal invasion 1 mm or less in diameter is defined as DCIS with microinvasion, DCIS-Mi. Identification of biological differences between DCIS and DCIS-Mi may aid in understanding of the nature and causes of the progression of DCIS to invasiveness.
In this study, using resected breast cancer tissues, we compared pure DCIS (52 cases) and DCIS-Mi (28 cases) with regard to pathological findings of intraductal lesions, biological factors, apoptosis-related protein expression, and proliferative capacity through the use of immunohistochemistry and the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method.
There were no differences in biological factors between DCIS and DCIS-Mi, with respect to levels of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor type 2. The frequency of necrosis and positive expression ratio of survivin and Bax were significantly higher in DCIS-Mi than in DCIS. In addition, apoptotic index, Ki-67 index, and positive Bcl-2 immunolabeling tended to be higher in DCIS-Mi than in DCIS. Multivariate analysis revealed that the presence of necrosis and positive survivin expression were independent factors associated with invasion.
Compared with DCIS, DCIS-Mi is characterized by a slightly elevated cell proliferation capacity and enhanced apoptosis within the intraductal lesion, both of which are thought to promote the formation of cell necrotic foci. Furthermore, the differential expression of survivin may serve in deciding the response to therapy and may have some prognostic significance.
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