臺灣大學: 分子醫學研究所蘇怡寧李祐慈Li, Yu-TzuYu-TzuLi2013-03-202018-07-092013-03-202018-07-092012http://ntur.lib.ntu.edu.tw//handle/246246/247373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。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).4276826 bytesapplication/pdfen-US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Breast cancerIHCFISHaCGH[SDGs]SDG3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Application of array CGH in breast cancer oncology :comparison with IHC and FISHthesishttp://ntur.lib.ntu.edu.tw/bitstream/246246/247373/1/ntu-101-P99448002-1.pdf