在非小細胞肺癌病人中，酪胺酸激脢抑制劑治療效果與表皮生長因子受體是否有基因突變有重要關聯。位於exon 19與exon 21的基因突變約佔了表皮生長因子受體基因突變的九成，其中又分別以delE746-A750及L858R突變為主。此篇研究，我們以delE746-A750及L858R兩種的表皮生長因子受體突變特異抗體來偵測表皮生長因子受體基因突變及探討與治療結果的相關性。43位非小細胞肺癌病人，25位(58.1%)有表皮生長因子受體基因突變，delE746-A750基因突變有7位，L858R基因突變有18位。以表皮生長因子受體突變特異抗體檢驗出delE746-A750基因突變有4位，L858R基因突變有12位。以免疫組織化學染色方法來偵測表皮生長因子受體基因突變的敏感性及特異性，對delE746-A750突變為57.1% 及97.3%，對L858R突變為66.7% 及100%。陽性預測率及陰性預測率，對delE746-A750突變為80% 及94.7%，對L858R突變為100% 及80.6%。以免疫組織化學染色方法來分析治療結果，對平均無進展生存期沒有意義，但對平均整體存活期有意義。表皮生長因子受體突變特異抗體來偵測表皮生長因子受體突變有著高陽性預測率及高特異性的優點，如此可用來當作表皮生長因子受體基因突變的初步篩檢，如此在一般的病理檢驗時即可施行。此外，對於整體存活率也有預測價值。

Efficacy of tyrosine kinase inhibitor (TKI) therapy depends on epidermal growth factor receptor (EGFR) mutation status in patients with non-small cell lung cancer (NSCLC). There has been an increasing interest in studying mutation-specific rabbit monoclonal antibodies of delE746-A750 mutation in exon 19 and L858R point mutation in exon 21 for detecting EGFR mutants. These two mutations account for approximately 90% of all EGFR mutations. We evaluated the two mutation-specific monoclonal antibodies for the detection of EGFR mutations by immunohistochemistry (IHC) and the relationship with treatment outcome and survival. Twenty-five patients (58.1%) harbored EGFR mutations. These mutations include delE746-A750 mutation for seven patients, L858R point mutation for in eighteen patients. IHC showed, for the delE746-A750 and L858R mutations, sensitivity (57.1% and 66.7%), specificity (97.3% and 100%), positive predictive value (80.0% and 100%), and negative predictive value (94.7% and 80.6%). Analysis for progression-free survival was not correlated to IHC staining, but the overall survival was correlated to IHC staining. These mutation-specific antibodies for delE746-A750 and L858R mutations have high positive predictive value and specificity for predefined EGFR mutations and may be suitable for screening for these predefined mutations. However, negative IHC results required further mutation analyses before excluding EGFR TKI therapy.

論文審定書…………………………………...………………………
致謝………………………………………………………………..…I
中文摘要………………………………………………………..........II-III
英文摘要………………………………………………….…...…..…IV-V
第一章 背景介紹
1.1 背景及動機……………………………………….........1-2
1.2 研究動機…………………………………………….….3
1.3 研究目標…………………………………………….….4
第二章 研究方法
2.1 病患篩選與治療…………………………………….…..5
2.2 DNA萃取……………………………………………..….6
2.3 聚合酵素鍊鎖反應擴增DNA…………………………..6
2.4 即時聚合酵素鍊鎖反應及DNA定序偵測表皮生長
因子受體基因突變……………………………………..7
2.5 免疫組織化學染色偵測表皮生長因子受體基因突變..7-8
2.6 統計分析…………………………………….…………. 8
第三章 結果分析
3.1 病患特性及表皮生長因子受體酪胺酸激脢抑制劑治療
效果…………………………………….……………9-10
3.2 表皮生長因子受體基因突變分析…………………..10
3.3 表皮生長因子受體基因突變與治療結果分析……..10-11
3.4 表皮生長因子受體基因突變對存活率上的影響…..11-12
3.5 以分子生物技術及免疫組織化學染色方法偵測表皮生
長因子受體基因突變的比較……………………….12-13
3.6 以突變特異抗體染色結果來預測酪胺酸激脢抑制劑治
療效果…………………………………...…………..13
第四章 討論分析…………………………………...……………..14-18
第五章 結論…………………………………...…………………..19
表格…………………………………...…………………..…………20-31
圖次…………………………………...…………………………..…32-39
參考文獻…………………………………...………………………..40-46
附錄…………………………………...…………………..…………47

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