臺灣博碩士論文加值系統

背景：血管生成是腫瘤生長和轉移所必須的。依據前人之研究，血管生成和乳癌，肺癌，前列腺癌和其他癌之腫瘤大小、轉移潛力或預後有關。相同的研究結果也發現於頭頸部癌，但結果並不一致。本研究之目的在探討血管生成是否發生於嚼檳榔和吸菸相關的口腔癌前病變及口腔鱗狀細胞癌(OSCC)中。
方法：本研究利用anti-CD31免疫組織化學染色，研究76例OSCC，40例口腔上皮過度角化(OEH)， 38例口腔上皮變異(OED)， 41例口腔黏膜下纖維化症(OSF)和11例正常口腔黏膜(NOM)標本中之血管生成。計算OSCC， OEH， OED， OSF和NOM標本中之平均微細血管數目(Microvessel count, MVC)並互相比較。同時分析OSCC之MVC和OSCC患者臨床和病理參數之相關性。
結果：NOM， OEH， OED和OSF於口腔黏膜固有層之平均MVC分別為13.2±5.1，17.7±6.8，27.8±10.0和12.4±6.3。OED之平均MVC大於OEH( P<0.001)，NOM( P<0.001)和OSF( P<0.001)之平均MVC。且OEH之平均MVC，大於NOM( P<0.05)和OSF( P<0.001)之平均MVC。但NOM之平均MVC和OSF之平均MVC沒有明顯差別。OSCC之平均MVC於腫瘤邊緣為43.7±18.9，於腫瘤中央為10.2±4.8。就OSCC腫瘤邊緣之平均MVC而言: 女性患者高於男性患者，無吸菸患者高於吸菸患者， 無接受手術前化學治療患者高於有接受手術前化學治療患者，存活患者高於死亡患者。利用Kaplan-Meier曲線分析，發現腫瘤邊緣MVC>40 OSCC患者之存活率比腫瘤邊緣MVC<40 OSCC患者之存活率為高。另外無接受手術後放射線治療OSCC患者之存活率，比有接受手術後放射線治療 OSCC 患者之存活率較高。
結論：明顯增加之血管生成開始於口腔癌生成過程的早期(口腔癌前病變時期)，當NOM轉變成OEH和OED時，血管生成逐漸增加，至演變成口腔癌時，血管生成突然增加到最大程度。但我們目前所用之血管生成計算法並無法有效的預測嚼檳榔和吸菸相關口腔鱗狀細胞癌之轉移潛力，腫瘤大小和臨床分期。

Background : Angiogenesis is necessary for tumor growth and metastasis. lt has been shown to correlate with tumor size, metastatic potential or prognosis in breast , lung, prostate and other cancers. Studies in head and neck cancers have suggested a similar correlation, but results have been inconclusive . This study was performed to determine whether angiogenesis occurs in oral premalignant lesions and oral squamous cell carcinomas. (OSCCs) in betel nut chewers and tobacco smokers.
Method : This study used anti-CD31(anti-JC/70A) immunostaining to study the angiogenesis in 76 specimens of OSCC, 40 specimens of oral epithelial hyperkeratosis (OEH), 38 specimens of oral epithelial dysplasia (OED), 41 specimens of oral submucous fibrosis (OSF), and 11 specimens of normal oral mucosa (NOM). The mean microvessel counts (MVCs) in specimens of OSCC , OEH, OED, OSF and NOM were compared. In addition, MVCs in OSCCs were further correlated with the clinicopathological parameters of OSCC patients.
Results：The mean MVC in the lamina propria of oral mucosa was 13.2±5.1 for NOM, 17.7±6.8 for OEH, 27.8±10.0 for OED and 12.4±6.3 for OSF. The mean MVC of OED was significantly higher than those of OEH ( P<0.001), NOM ( P<0.001) and OSF ( P<0.001). Furthermore, the mean MVC of OEH was significantly greater than those of NOM ( P<0.05) and OSF ( P<0.001). However, there was no significant difference in mean MVC between NOM and OSF ( P>0.05). The mean MVC in specimens of OSCC was 43.7±18.9 in tumor periphery ( TP) and 10.2±4.8 in tumor center( TC). Significantly higher mean MVC in TP was found in female than in male patients ( P<0.05), in non-smoker than in smoker patients ( P<0.05), in patients who did not receive pre-operative chemotherapy than in those who received pre-operative chemotherapy ( P<0.05), and in patients who still survived than in those who died of OSCC ( P<0.05).Kaplan-Meier analysis showed that the prognosis for OSCC patients with MVC of TP>40 was significantly better than that for patients with MVC of TP<40. In addition, the prognosis for OSCC patients without post-operative radiotherapy was also better than that for patients with post-operative radiotherapy.
Conclusion：Significantly elevated angiogenesis began at the early stage of oral carcinogenesis (the premalignant lesion stage). The angiogenesis increased gradually as the NOM transformed to OEH and to OED. It increased abruptly to the greatest extent in OSCC. However , angiogenesis , as currently measured , is not of value in predicting the metastatic potential, tumor size and clinical stages of the betal quid chewing and smoking-related OSCC.

表目錄……………………………………………………………………….Ⅰ
圖目錄……………………………………………………………………….Ⅱ
中文摘要……………………………………………………………………. 1
英文摘要……………………………………………………………………. 3
壹、緒論……………………………………………………………………. 5
前言………………………………………………………………………….7
貳、文獻回顧………………………………………………………………. 9
一、台灣口腔癌…………………………………………………………… 9
二、口腔癌前病變……………………………………………………… 12
三、腫瘤血管生成………………………………………………………… 15
四、口腔癌及頭頸部癌血管之生成……………………………………….28
五、免疫組織化學染色法……………………………………………….. 34
參、材料與方法……………………………………………………………. 35
一、研究個案標本選取……………………………………………….. 35
二、標本固定與包埋………………………………………………….. 36
三、實驗方法………………………………………………………….. 37
四、免疫組織化學染色後之觀察與記錄……………………………. 40
五、臨床分期與臨床評估……………………………………………… 41
六、統計分析…………………………………………………………….. 42
肆、結果…………………………………………………………………….43
伍、討論…………………………………………………………………….46
陸、結論…………………………………………………………………….53
柒、附表與附圖…………………………………………………………….54
捌、參考文獻……………………………………………………………….66

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