- Expression of Matrix Metalloproteinase and Tissue Inhibitor of Metallproteinase in Breast Carcinoma Related to Angiogenesis and Invasion.
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Yoon Jung Choi, Woo Hee Jung, Hy De Lee, Kwang Gil Lee
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Korean J Pathol. 2000;34(9):652-664.
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- Among the enzymes which are responsible for basement membrane breakdown, matrix metalloproteinases (MMP) form a family of neutral proteases that are regulated at the levels of gene transcription, proenzyme activation by the cleavage of protein, and the inhibition of the active enzyme by tissue inhibitors of matrix metalloproteinases (TIMP). Recent reports have demonstrated that the expression of these proteolytic enzymes are elevated in several solid tumors and that it can be associated with invasiveness and poor prognosis. We examined the expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 by immunohistochemistry in 160 cases of infiltrating ductal carcinoma. And we compared these data with the established prognostic parameters - tumor size, nodal status, clinical stage, hormonal receptor status, microvessel density, and TGF-beta1 expression in order to evaluate how MMP and TIMP expression are associated with breast cancer progression and prognosis.
Microvessel density in invasive breast carcinoma was significantly correlated with tumor size and recurrence (p<0.05).
The immunohistochemical expression of TGF-beta1 was significantly associated with tumor size, lymph node metastasis, and clinical stage (p<0.05).
The microvessel density was significantly correlated with TGF-beta1 expression in more than 50% of tumor cells. The immunohistochemical expression of MMP-2 and MMP-9 were significantly correlated with nodal metastasis and absence of immunoreactivity for estrogen and progesterone receptors. The immunohistochemical expression of TIMP-1 was inversely correlated with clinical stage and microvessel density while that of TIMP-2 was inversely correlated with clinical stage (p<0.05). Small size of tumor, presence of progesterone receptor, highly differentiated histologic grade, and absence of immunoreactivity for MMP-9 were significantly associated with higher survival rate, but in multivariate analysis only tumor size and MMP-9 expression appeared to affect survival independently.
- Expression of Biologic Markers and DNA Ploidy Analysis in Atypical Ductal Hyperplasia and Ductal Carcinoma in Situ of the Breast.
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Hee Jung Kim, Woo Hee Jung, Hyeon Joo Jeong, Hy De Lee
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Korean J Pathol. 1999;33(11):1076-1089.
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Abstract
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- Status of margins and the size of the lesion are independent prognostic factors of ductal carcinoma in situ (DCIS). Histologic grading of DCIS and expression of biologic marker also appear to act as prognostic factors. However, DNA ploidy analysis using flow cytometry in the DCIS and atypical ductal hyperplasia (ADH) has been rarely reported, and the biologic behavior of ADH is unknown. We performed immunohistochemical staining and DNA ploidy analysis using flow cytometry on 45 cases of pure DCIS without microinvasion and 34 cases of ADH to compare the expression of biologic markers and DNA ploidy patterns according to the histologic grade of DCIS, to evaluate the usefulness of the Van Nuys classification, and to investigate the biologic behavior of ADH and low grade DCIS.
A total of 41.9% of DCIS and 32.1% of ADH were detected mammographically in asymptomatic patients. The most common subtype of the high grade DCIS was comedo type (56.3%), while the low and intermediate grade DCIS were cribriform type. Expression of ER, c-erbB-2 and Ki-67 proliferative index (PI) was significantly associated with nuclear grade and histologic grade of DCIS. Expression of c-erbB-2 was also significantly correlated with presence of necrosis. In low grade DCIS, Ki-67 PI was significantly higher than ADH. A total of 63.6% of DCIS and 70% of ADH were diploidy and 15.9% of DCIS was aneuploidy. There was no aneuploidy in ADH. No significant association was noted between DNA ploidy and histologic grade or nuclear grade. However, in high grade DCIS, the frequency of aneuploidy was high. In conclusion, histologic grading of DCIS employing nuclear grade and necrosis is a useful tool accounting for biologic behavior.
High grade DCIS and comedo DCIS impart aggressive biologic behavior and suggest a higher possibility of local recurrence or progression to invasive carcinoma. In the differential diagnosis of ADH and low grade DCIS, the use of Ki-67 PI and DNA ploidy analysis by flow cytometry will be helpful for accurate diagnosis and prediction of biologic behavior.
- DNA Ploidy Analysis as a Prognostic Indicator in Phyllodes Tumor of the Breast.
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Hee Jung Kim, Jae Ho Han, Woo Hee Jung, Hy De Lee
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Korean J Pathol. 1999;33(7):507-516.
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Abstract
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- DNA ploidy analysis using flow cytometry was performed on sixty six cases of phyllodes tumor of the breast including benign, low grade and high grade malignant phyllodes tumor. The rate of aneuploidy was 41.2% in high grade malignant phyllodes tumor and 4.8% in benign phyllodes tumor. No aneuploidy was noted in low grade malignant phyllodes tumor. The recurrence rate according to DNA ploidy pattern revealed 16.7% of aneuploidy and 7.7% of diploidy. In the aneuploid cases, the DNA index of high grade malignant phyllodes tumor was higher than benign phyllodes tumor.
Morever, in diploid cases, %SG2M were significantly higher in high grade malignant phyllodes tumor. Therefore, we conclude that DNA ploidy analysis as well as histologic characteristics such as cellularity, pleomorphism of stromal cells and mitoses is useful parameters in the diagnosis, recurrence and prognostic predictors of phyllodes tumor.
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