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|Title:||Polysomy of Chromosome 17: Its Clinicopathological Significance in Breast Cancer Female Patients in Kuwait||Authors:||Farah M.Anwar Bakhsh||Supervisor:||Dr. Issam M.Francis||Keywords:||Breast cancer;Her-2/neu Amplification;Polysomy 17;Immunohistoschemistry;FISH||Issue Date:||2012||Publisher:||Kuwait university - college of graduate studies||Abstract:||Amplification of the HER-2/neu gene is one of the established prognostic markers that leads to protein overexpression in 25-30% of breast cancer cases. A subset of breast carcinoma showed polysomy of chromosome 17, which is encountered frequently during the assessment of HER-2/neu status. Unlike gene amplification, the role of polysomy 17 is uncertain. The hypothesis of this study is that polysomy 17, compared to HER-2/neu positive and HER2/neu negative, has a distinct impact on the clinicopathological features of breast cancer and it can be considered as a useful prognostic marker for breast tumor. We also hypothesized that polysomy 17 is an indirect mechanism that contributes to increased numbers of HER-2/neu gene resulting in protein overexpression in the absence of gene amplification. Therefore, 271 archival, formalin-fixed, paraffin-embedded blocks of breast cancer were collected. Expressions of ER, PR, Ki-67 and overexpression of HER-2/neu were studied using immunohistochemical method. The FISH assay was used to determine HER-2/neu gene amplification. The frequency of polysomy 17 was 13.6%. In relation to the anatomical site, stage, and histopathological type of the tumor, a statistically significant difference was observed between polysomy 17 and HER-2/neu negative. In addition, the ER status and PR status of polysomy 17 differed from those of HER-2/neu positive, and these differences were associated with hormone receptor positivity. Patients with polysomy 17 were also found to have the shortest OS (P = 0.001) and a trend toward shorter DFS. A highly significant association was observed between polysomy 17 and HER2/neu protein overexpression (P = 0.000) with a score of 2+ by IHC. These results suggest that polysomy 17 can be characterized as having different v clinicopathological features from either HER-2/neu positive or HER-2/neu negative tumors. Our results also showed that polysomy 17 has a significant biological influence on HER-2/neu protein overexpression and that it can be considered as a prognostic marker in breast cancer.||URI:||http://hdl.handle.net/123456789/177|
|Appears in Programs:||0570 Pathology (M.Sc.)|
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