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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 蘇怡寧 | |
dc.contributor.author | Yu-Tzu Li | en |
dc.contributor.author | 李祐慈 | zh_TW |
dc.date.accessioned | 2021-06-16T17:38:53Z | - |
dc.date.available | 2013-09-18 | |
dc.date.copyright | 2012-09-18 | |
dc.date.issued | 2012 | |
dc.date.submitted | 2012-08-15 | |
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Implementation of American Society of Clinical Oncology/College of American Pathologists HER2 Guideline Recommendations in a tertiary care facility increases HER2 immunohistochemistry and fluorescence in situ hybridization concordance and decreases the number of inconclusive cases. Arch Pathol Lab Med. 2009 May;133(5):775-80. 14. Nagata Y, Lan KH, Zhou X, Tan M, Esteva FJ, Sahin AA, Klos KS, Li P, Monia BP, Nguyen NT, Hortobagyi GN, Hung MC, Yu D. PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients. Cancer Cell. 2004 Aug;6(2):117-27. 15. Parker JS, Mullins M, Cheang MC, Leung S, Voduc D, Vickery T, Davies S, Fauron C, He X, Hu Z, Quackenbush JF, Stijleman IJ, Palazzo J, Marron JS, Nobel AB, Mardis E, Nielsen TO, Ellis MJ, Perou CM, Bernard PS. Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol. 2009 Mar 10;27(8):1160-7. 16. 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Direct-to-consumer personal genomic testing: a case study and practical recommendations for “genomic counseling”. J Genet Couns. 2012 Jun;21(3):402-412. 20. Tafe, Laura J,Tsongalis, Gregory J. The human epidermal growth factor receptor 2 (HER2). Clin Chem Lab Med.2012 Sep 50(1):23-30 21. Tse CH, Hwang HC, Goldstein LC, Kandalaft PL, Wiley JC, Kussick SJ, Gown AM. Determining True HER2 Gene Status in Breast Cancers With Polysomy by Using Alternative Chromosome 17 Reference Genes: Implications for Anti-HER2 Targeted Therapy. J Clin Oncol. 2011 Nov 1;29(31):4168-74 22. Vig HS, Wang C.The evolution of personalized cancer genetic counseling in the era of personalized medicine. Fam Cancer. 2012 Mar 15. 23. Wang J, Saukel GW, Garberoglio CA, Srikureja W, Hsueh CT. Pathological complete response after neoadjuvant chemotherapy with trastuzumab-containing regimen in gastric cancer: a case report. J Hematol Oncol. 2010 Sep 9;3:31. 24. Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, McShane LM, Paik S, Pegram MD, Perez EA, Press MF, Rhodes A, Sturgeon C, Taube SE, Tubbs R, Vance GH, van de Vijver M, Wheeler TM, Hayes DF; American Society of Clinical Oncology; College of American Pathologists. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 2007 Jan 1;25(1):118-45. 25. Yang YL, Fan Y, Lang RG, Gu F, Ren MJ, Zhang XM, Yin D, Fu L. Genetic heterogeneity of HER2 in breast cancer: impact on HER2 testing and its clinicopathologic significance. Breast Cancer Res Treat. 2012 Apr 5. 26. Yeh IT, Martin MA, Robetorye RS, Bolla AR, McCaskill C, Shah RK, Gorre ME, Mohammed MS, Gunn SR. Clinical validation of an array CGH test for HER2 status in breast cancer reveals that polysomy 17 is a rare event. Mod Pathol. 2009 Sep;22(9):1169-75. 27. Yildiz-Aktas IZ, Dabbs DJ, Bhargava R. The effect of cold ischemic time on the immunohistochemical evaluation of estrogen receptor, progesterone receptor, and HER2 expression in invasive breast carcinoma. Mod Pathol. 2012 Mar 30. doi: 10.1038 | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/64288 | - |
dc.description.abstract | 目前已知約有15~25%左右的乳癌病人具有HER2 基因擴增的情況,針對HER2 基因擴增的陽性患者,目前臨床上已有標靶藥物如Transtuzumab(Herceptin)、Lapatinib(Tykerb)可使用,並延緩復發及惡化的時間,因此乳癌患者針對病理檢體進行HER2 基因的檢測是決定治療計畫的重要依據。
HER2 基因臨床上最常見的檢測的方式為免疫組織化學染色法(Immunohistochemistry;IHC),其優點在於檢驗時間短,成本便宜,缺點在於其利用染色後的顏色深淺做判讀,受限於判讀者的主觀判斷,同時檢測結果無法量化。另一種方式為螢光原位雜交法(Fluorescent in-situ hybridization;FISH),常見於當免疫組織化學染色法無法精確判讀HER2 基因是否為陽性時使用,其原理為比較第17 對染色體HER2 基因劑量與第17 對染色體中節位置的基因劑量,依據兩者的比值大小判定檢測結果。然而,目前已知針對如第17 對染色體為多倍體的病人,採用螢光原位雜交法可能產生偽陰性的結果;若第17 對染色體中節大片段缺失,使得分母過小,也可能導致偽陽性的結果。根據美國臨床腫瘤學會(American Society of Clinical Oncology;ASCO)在西元2007 年發表的乳癌HER2 基因檢測指引中指出,目前約有20% HER2的基因檢測結果可能是不正確的(Wolff AC et al 2007),而在西元2009 年另一篇文獻表示經依照HER2 檢測指引後,免疫組織化學染色(Immunohistochemistry;IHC)與螢光原位雜交法(Fluorescent in-situ hybridization;FISH)的一致率已達98%(Middleton LP et al 2009),高於指引所要求的一致率95%。 為了解HER2 基因在第17 對染色體上的的真實面貌,運用新的分子診斷技術-晶片式全基因體定量分析術(Array Comparative Genomic Hybridization;aCGH),與現有技術進行比較分析,期望能在未來對於HER2 基因的檢測上,提供另一種分子檢驗技術的選擇。 此外,由於晶片式全基因體定量分析術(Array Comparative Genomic Hybridization;aCGH)的優點在於可同時進行全基因體掃描,隨著個人化醫療時代的來臨,基因檢測將是未來的趨勢,不同腫瘤上特殊的基因擴增或缺失,對於新興藥物開發以及癌症治療上,皆有相當重要的意義。藉由晶片式全基因體定量分析術(Array Comparative Genomic Hybridization;aCGH)的優勢,對於未來癌症研究應有莫大的助益。 | zh_TW |
dc.description.abstract | Currently, we have known that about 15%~25% of breast cancer patients have HER2 gene amplification. For these patients, the present study demonstrated that drugs such as Transtuzumab(Herceptin), Lapatinib (Tykerb) can be used to delay the recurrence and progression. Therfore, the detection of HER2 has become a very important test to determine the treatment plan for breast cancer patients.
The most common HER2 gene test is immunohistochemical staining(Immunohistochemistry;IHC), which is faster and cheaper in testing. However, its major disadvantages are that the results are hardly quantified and just determined by the color density, which is judged by the interpreter’s subjective opinions. Another technique is Fluorescent in-situ hybridization(FISH) which is used when the immunohistochemical staining(IHC) revealed equivocal(2+). The method of Fluorescent in-situ hybridization(FISH) is dectecting the ratio of the HER2 gene expression in chromosome 17 over the gene expression in the centromere. However, it is known that FISH will produce false negative in those patients with chromosome 17 polypoidy or fales positve in those patients with a large number of deletion in centromere in chromosome 17. According to breast cancer HER2 gene testing guidelines published by the American Society of Clinical Oncology (ASCO) in 2007, there are about 20% HER2 gene test results may be incorrect. (Wolff AC et al 2007)However ,another reference published in 2009 indicated that the concordance between IHC and FISH has been up to 98%(Middleton LP et al 2009), which is better than the requirements(95%) in the guideline. In order to understand the role of HER2 gene in chromosome17 , we can utilize the new molecular diagnostic techniques, Array Comparative Genomic Hybridization(aCGH), providing another choice to detect HER2 gene. It can screen the whole genome in the same time. Thus, with the time of personalized medicine comes, gene detection will be the medical trends. It is significant that the specific gene amplification or deletion in variant tumors is associated with the new drug development and the treatments. As a result, it will be extremely helpful for the cancer researches in the future by the Array Comparative Genomic Hybridization(aCGH). | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T17:38:53Z (GMT). No. of bitstreams: 1 ntu-101-P99448002-1.pdf: 4276826 bytes, checksum: 11438bd96ef5c071880b30328036c9b1 (MD5) Previous issue date: 2012 | en |
dc.description.tableofcontents | 第一章 研究背景與動機p.1
1.1乳癌的流行病學p.1 1.2乳癌的發生學p.1 1.2.1致癌物(carcinogen) 1.2.2 乳癌敏感基因(breast cancer susceptibility gene) 1.3乳癌的病理分類p.2 1.4乳癌的癌症分期p.3 1.5影響乳癌治療與預後之重要影響因子p.4 1.6乳癌基因表現分子分類p.5 1.7 Her-2基因介紹p.6 1.8 Her-2基因檢測方式p.7 1.8.1免疫組織化學染色法(Immunohistochemistry;IHC) 1.8.2螢光原位雜交法(Fluorescent in-situ hybridization;FISH) 1.9研究動機p.11 第二章 研究方法p.12 2.1研究樣本p.12 2.2實驗室材料與試劑p.12 2.2.1 BAC array CGH 晶片 2.2.2 Oligo array CGH 晶片 2.3實驗方法p.13 2.3.1 DNA 萃取 2.3.2 晶片式全基因體定量分析術 2.3.3 基因劑量判讀 第三章 研究結果p.15 3.1.IHC 檢測為0+與Array CGH 檢測結果一致性分析p.15 3.2.IHC 檢測為1+與Array CGH 檢測結果一致性分析p.16 3.3 IHC 檢測為 2+與FISH 和Array CGH 檢測結果一致性分析p.20 3.4 Neoadjuvant C/T 前後IHC 分別檢測為 0+、2+與Array CGH 檢測結果一致性分析p.25 3.5 IHC 檢測為 3+與Array CGH 檢測結果一致性分析p.26 3.6 IHC 、FISH、Array CGH綜合比較p.29 第四章 討論p.32 4.1全基因體定量分析術(Array-comparative genomic hybridization;aCGH)釐清第17對染色體確切的基因劑量表現p.32 4.2利用全基因體定量分析術(Array-comparative genomic hybridization;aCGH)進行腫瘤基因變異分析p.35 4.3尋找其他可能的乳癌的分子生物標記p.39 4.4晶片式全基因體定量分析術(Array comparative genomic hybridization;aCGH)於其他癌症分子生物學上之應用p.40 第五章 結論p.41 5.1 乳癌商業化分子診斷平台p.41 5.2 癌症遺傳諮詢的定位與角色p.42 5.3 基因檢測之遺傳諮詢與倫理省思p.44 第六章 參考文獻p.45 | |
dc.language.iso | zh-TW | |
dc.title | 晶片式全基因體定量分析術於乳癌腫瘤學之應用:與免疫組織化學染色法及螢光原位雜交法之比較 | zh_TW |
dc.title | Application of array CGH in breast cancer oncology :comparison with IHC and FISH | en |
dc.type | Thesis | |
dc.date.schoolyear | 100-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 楊偉勛,黃俊升,連晃駿 | |
dc.subject.keyword | 乳癌,HER2,免疫組織染色法,螢光原位雜交法,晶片式全基因體定量分析術, | zh_TW |
dc.subject.keyword | Breast cancer,HER2,IHC,FISH,aCGH, | en |
dc.relation.page | 101 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2012-08-15 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 分子醫學研究所 | zh_TW |
顯示於系所單位: | 分子醫學研究所 |
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