Article

DCIS Prognostic Markers: A Few New Candidates Emerge

Journal of the National Cancer Institute (Impact Factor: 12.58). 05/2010; 102(9):588-90. DOI: 10.1093/jnci/djq161
Source: PubMed

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Available from: jnci.oxfordjournals.org
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    ABSTRACT: Abstract This report describes a case of ductal carcinoma in situ (DCIS) that regressed after treatment with acupuncture, Chinese herbs, and other complementary and alternative medicine (CAM). The natural history of DCIS remains to be elucidated, and it is unclear whether all DCIS cases progress to invasive breast cancer. Surgery plus radiation therapy or mastectomy is recommended for women in whom this potentially nonprogressive cancer is detected. This case supports the developing trend toward active surveillance in lieu of breast-disfiguring surgery and offers evidence that CAM therapies may be of value in preventing progression of DCIS to invasive breast cancer.
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    ABSTRACT: Background: Fibroblast growth factor-2 (FGF-2) supports tumor progression in breast cancer. FGF-2 signaling is modulated by heparan sulfate proteoglycans, such as syndecan-1 (CD138). The exact role of CD138 in ductal carcinoma in situ of the breast (DCIS) is still uncertain. Differential expression depending on grading could suggest a role for syndecan-1 during growth and tumor progression. Materials and methods: Samples of 127 cases of breast DCIS associated with follow-up data were included. CD138 staining intensity, number of positive cells, intracellular and tissue localization were examined. Results: Median follow-up was 45.4 months and median recurrence-free survival (RFS) 86 months. Age, menopausal status and previous hormone replacement therapy had no significant influence on RFS. Smoking significantly influenced RFS (p=0.008). Endocrine therapy or radiotherapy did not improve RFS. Grading was not correlated with CD138 staining intensity, but was significantly associated with the percentage of CD138-positive cells (low-vs. high-grade, p=0.043). Estrogen receptor (ER) expression did not influence staining intensity of CD138 (p=0.247), but negatively correlated with the proportion of CD138-positive cells (p=0.032). Progesterone receptor (PR) expression significantly influenced the intensity of staining (p=0.010) and the percentage of CD138-positive cells (p=0.004); both were increased in PR-negative cases. CD138 staining intensity and percentage of positive cells did not correlate with RFS. Nuclear grade and syndecan-1 staining localization were significantly associated (p=0.001). ER-positive, and PR-positive DCIS more often exhibited membrane-bound syndecan-1 than ER- or PR-negative cases (p=0.001). Nuclear grade and tissue localization of CD138 correlated significantly (p=0.005). PR influenced CD138 tissue distribution, while ER did not. Syndecan-1 localization did not statistically impact RFS. Conclusion: In DCIS of different nuclear grades, tissue localization of syndecan-1 is significantly divergent, suggesting a specific effect on biology and progression of DCIS.
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    ABSTRACT: The tumor microenvironment dynamically regulates the progression of cancer. In the breast, a unique component of the microenvironment is the myoepithelial cell. Normal myoepithelial cells act as "natural tumor suppressors"; however, more recent evidence suggests that these cells develop phenotypic changes, which may contribute to loss of tumor suppressor activity. We have shown that myoepithelial cells in a subset of preinvasive ductal carcinoma in situ (DCIS) upregulate expression of the integrin αvβ6, switching on tumor promoter activity through activation of TGFβ and MMP9. This makes the tumor microenvironment more permissive to invasion, seen both in vitro and in vivo. In human tissue samples, increased myoepithelial αvβ6 expression correlated with increased risk of disease progression and recurrence. Current estimates suggest that as many as 50% of DCIS cases will never progress in the patient's lifetime, but there are no markers to predict the outcome of individual cases. The identification of αvβ6 in a subset of DCIS presents a unique way to stratify patients with DCIS into those who may or may not progress to more serious disease. As αvβ6 is not expressed on most normal adult tissues, this finding may also provide novel targets for therapy in this high-risk group. Cancer Res; 74(21); 1-6. ©2014 AACR.
    Full-text · Article · Oct 2014 · Cancer Research