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Breast Cancer Stem Cells And Breast Cancer Prognosis, And Notch Pathway

Posted on:2011-07-21Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y ZhongFull Text:PDF
GTID:1114360305967958Subject:Surgery
Abstract/Summary:PDF Full Text Request
Part1The Association between Breast Cancer Stem cell and Clinical OutcomePurpose:To investigate the relevance between clinical prognosis and breast cancer stem cell with CD44+/CD24- characteristics. To investigate the relevance between clinical prognosis and breast cancer stem cell with ALDH1-positive characteristics.Methods:Primary breast cancer patients (n=121) treated in Peking Union Medical College Hospital were included in the study. The study included paraffin embedded tissue of 121 patients with primary lesion. CD44+/CD24-tumor cell proportions were detected by double-staining immunofluorescence and ALDH1 tumor cells were detected by immunohistochemistry.Results:There was no significant correlation between CD44+/CD24-cell and other clinical characteristics.There was no significant correlation between CD44+/CD24-cell and tumor progression. The association can not be demonstrated between ER(-)HER-2(-) breast cancer and CD44+/CD24- cell. There was no significant correlation between CD44+/CD24" cell and clinical prognosis. There was no significant correlation between ALDH1 and other clinical characteristics. The association can not be demonstrated between ER(-)HER-2(-) breast cancer and ALDH1. There was no significant difference of CD44+/CD24- cell proportions between ALDH1-positive breast cancer and ALDH1-negtive breast cancer. There was no significant correlation between ALDH1 and clinical prognosis.Conclusion:Prevelence of CD44+/CD24" tumor cell or ALDH1 may not be associatied with clinical outcome and disease-free survival. There was no significant correlation between tumor stem cell identified by CD44+/CD24- and ER(-)HER-2(-) breast cancer. There was no significant correlation between tumor stem cell identified by ALDH1 and ER(-)HER-2(-) breast cancer. Part 2The Association between Breast Cancer Stem Cell and Recurrence,MetastasisPurpose:To detect the CD44+/CD24-tumor cell proportions difference between primary lesion and recurrence lesion. To detect the ALDH1-positive tumor cell difference between primary lesion and recurrence lesion.Methods:Primary breast cancer patients (n=121) treated in Peking Union Medical College Hospital were included in the study. The study included paraffin embedded tissue of 27 patients with primary lesion and 27 patients with recurrence lesion. CD44+/CD24- tumor cell proportions were detected by double-staining immunofluorescence and ALDH1 tumor cells were detected by immunohistochemistry.Results:Although CD44+/CD24-cell proportions was higher in recurrence lesion, compared with primary lesion, there was no significant difference between two teams. Although the percentage of ALDH1-positive in recurrence lesion was higher, compared with primary lesion, there was no significant difference between two teams. The extent of ALDH1(+) positive of primary lesion in patients with recurrence or metastasis was higher, compared with patients without recurrence or metastasis. It suggest that breast cancer with ALDH1-positive may be associated with tumor progression.Conclusion:ALDH1 may be associated with tumor progression. Part 3The Association between NOTCH Signaling Pathway and Breast Cancer Stem CellPurpose:To analyze the association between NOTCH signaling pathway and breast cancer stem cell with CD44+/CD24-characteristics. To analyze the association between NOTCH signaling pathway and breast cancer stem cell with ALDH1-positive characteristics.Methods:Primary breast cancer patients (n=43) treated in Peking Union Medical College Hospital were included in the study. The study included paraffin embedded tissue and fresh tissue. CD44+/CD24-tumor cell proportions were detected by double-staining immunofluorescence and ALDH1 tumor cells and NOTCH 1 were detected by immunohistochemistry. Evaluation was obtained by microscopic pathologic inspection and automated image analysis. NOTCH 1 m RNA was detected by real-time fluorogenetic quantitative PCR.Results:Although NOTCH 1 mRNA was higher in ALDH1-positive breast cancer compared with ALDH1-negative breast cancer and NOTCH 1 protein was higher in ALDH1-positive breast cancer, compared with ALDH1-negative breast cancer, there was no significant association between NOTH signaling pathway and breast cancer stem cell with ALDH1 characteristics. Although NOTCH1 mRNA was higher in patients with D44+/CD24-cell proportion=0%compared with patients with CD44+/CD24-cell proportion>0%, and NOTCH 1 protein was higher in patients with D44+/CD24-cell proportion=0%compared with patients with CD44+/CD24- cell proportion>0%, there was no significant association between NOTH signaling pathway and breast cancer stem cell with CD44+/CD24-Conclusion:The association can not be demonstrated between NOTCH signaling pathway and tumor stem cells identified by CD44+/CD24- or ALDH1.
Keywords/Search Tags:breast cancer stem cell, ALDH1, CD44~+/CD24~-, prognosis, recurrence, metastasis, NOTCH singaling pathway
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