臺灣博碩士論文加值系統

背景：上皮生長因子接受器（EGFR）屬於ErbB/HER家族中的接受器型酪胺酸激酶，EGFR的活化能夠引發許多下游的細胞內受質之激活作用，導致有絲分裂路徑和其他促進腫瘤發展的細胞活動開始作用。在許多不同的人類癌症中，包括口腔癌，EGFR有過度表現的情形。Src屬於非接受器型酪胺酸激酶，在腫瘤的進展中佔有重要的角色。在惡性腫瘤中，Src的活化可以調節細胞的轉化作用、增生、凋亡、血管生成作用、局部侵犯性和活動度。要使這些活動開始運作，Src必須與其他的細胞因子如：EGFR等交互作用以啟動一連串反應。
材料和方法：本研究利用免疫組織化學染色的方法，探討EGFR和Src於93例口腔鱗狀細胞癌（OSCC）中和16例正常口腔黏膜（NOM）中的表現。並利用卡方檢定(Chi-square test)及Kaplan-Meier存活率方法來分析EGFR和Src的表現與口腔鱗狀細胞癌患者的臨床病理參數與存活率之相關性。
結果：在93例口腔鱗狀細胞癌中，EGFR的陽性反應佔43例（46.24%），而Src的陽性反應佔64例（68.82%）。EGFR和Src的表現之間並無相關性。此外，EGFR與口腔鱗狀細胞癌患者的臨床參數與存活率，無統計學上有意義之相關性。然而，Src的表現與口腔鱗狀細胞癌患者之低存活率、較大腫瘤（T3和T4）、淋巴結轉移（N+）和較晚之腫瘤臨床分期（stage3和stage4），有統計學上之相關性（p＜0.05）。
結論：在本研究中，Src的表現與口腔鱗狀細胞癌患者相關之臨床參數以及存活率有相關，惟EGFR的表現與相關之臨床參數則無統計學上有意義之相關。結果顯示在口腔鱗狀細胞癌的進展中，Src的活化可能扮演一個重要的角色，其可以成為口腔癌預後的一個指標。

Background: Epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor of ErbB/HER family, which is expressed or highly expressed in a variety of human cancers, including oral cancer. EGFR activation induced activation of several downstream intracellular substrates, leading to mitogenic signaling and other tumor-promoting cellular activities. Src is a nonreceptor tyrosine kinase that are reported to be critical for cancer progression. In malignant cells, Src activation can mediate transformation, proliferation, apoptosis, angiogenesis, invasion, and motility. To carry out these activities, Src interacts with numerous cellular factor, including EGFR.
Materials and Methods: In this study, we examined the expression of EGFR and Src in 93 specimens of squamous cell carcinoma (OSCC) and 16 specimens of normal oral mucosa (NOM) by immunohistochemistry. The correlation between the expression of EGFR and Src in OSCCs and clinicopathological parameters or survival of OSCC patients was analyzed by Chi-square test and Kaplan-Meier survival analysis.
Results: Positive EGFR and Src staining were present in 43 cases (46.24%) and in 64 cases (68.82%) of OSCC, respectively. There was no inter-relationship between EGFR and Src. Besides, there was no significant association of EGFR expression with any of the clinicopathological parameters or survival of OSCC patients. However, a significant correlation was found between Src expression and OSCC in the aspect of lower survial rate (p=0.01967), larger tumor sizes (T3 and T4, p=0.01562), regional lymph node metastases (N1, N2 and N3, p=0.02888) and more advanced clinical stages (stage3 and stage4, p=0.00938).
Conclusion: In the present study, Src expression was correlated with some clinical factors and survival, but EGFR expression was not. These results suggest Src may play an important role in tumor progression and may be a prognostic factor for OSCC.

表目錄………………………………………………Ⅲ
圖目錄………………………………………………Ⅴ
中文摘要……………………………………………1
英文摘要……………………………………………2
壹、文獻回顧………………………………………3
一、口腔癌之概觀..........................3
（一）、全球口腔癌之流行病學..............3
（二）、台灣口腔癌之流行病學..............3
（三）、口腔癌相關之危險因子..............4
二、口腔鱗狀細胞癌之病理分類..............5
三、口腔鱗狀細胞癌之預後..................5
四、EGFR在腫瘤中的表現....................5
（一）、EGFR的結構........................5
（二）、EGFR的調節作用....................6
（三）、EGFR的活化機制與過度表現..........7
（四）、EGFR在腫瘤中的表現................8
（五）、EGFR與人類癌症的臨床相關性........9
（六）、EGFR在頭頸部鱗狀細胞癌中的表現....9
五、Src在腫瘤中的表現.................12
（一）、簡介..............................12
（二）、c-Src的結構和功能.................12
（三）、c-Src的調節作用...................13
（四）、Src激酶家族（SFK）在信號傳遞中的角色...14
（五）、c-Src與人類癌症的關係.............16
（六）、c-Src在頭頸部鱗狀細胞癌中的表現...17
貳、材料和方法……………………………………18
參、結果……………………………………………24
肆、討論……………………………………………35
伍、結論……………………………………………42
陸、附表與附圖……………………………………43
柒、參考文獻………………………………………62

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