臺灣博碩士論文加值系統

本研究主要利用免疫組織化學染色法，探討p53蛋白以及其相關蛋白p21、MDM2，和PCNA於55例齒源性角化囊腫、35例含齒囊腫及34例根尖囊腫之表現。
研究結果顯示，齒源性角化囊腫之p53、p21、MDM2及PCNA陽性反應細胞於內襯上皮中的分布，與含齒囊腫及根尖囊腫相比，有較集中表現於基底旁層的現象。p53、p21、MDM2及PCNA於齒源性角化囊腫之平均標記指數分別為20.8±16.2、15.3±12.1、27.9±18.3和31.7±17.1；於含齒囊腫之平均標記指數分別為13.4±12.9、16.9±15.3、20.8±15.7和24.5±20.4；於根尖囊腫之平均標記指數分別為9.9±9.2、10.4±7.6、23.3±18.0和16.2±13.5。齒源性角化囊腫之p53及PCNA平均標記指數明顯高於含齒囊腫及根尖囊腫。多室性齒源性角化囊腫之p53平均標記指數明顯低於單室性齒源性角化囊腫者（P＜0.05）；含齒囊腫囊壁中發炎程度與PCNA平均標記指數有明顯相關（P＜0.05），重度發炎者有較高的PCNA平均標記指數；內襯上皮內出現透明體的根尖囊腫，其p21平均標記指數較內襯上皮內無出現透明體的根尖囊腫為低（P＜0.05）；其他的齒源性角化囊腫、含齒囊腫及根尖囊腫之臨床與組織病理參數與p53、p21、MDM2及PCNA之平均標記指數皆無明顯相關。
雖然齒源性角化囊腫、含齒囊腫及根尖囊腫皆出現高p53染色率，但觀察其p53/p21/MDM2免疫染色表現型，推論大部分的齒源性角化囊腫、含齒囊腫及根尖囊腫無p53基因突變發生。而p21及MDM2在p53＋及p53－的齒源性角化囊腫、含齒囊腫及根尖囊腫中均可被偵得，顯示在齒源性囊腫中p21及MDM2的表現除了以p53依賴途徑誘導產生外，也部分以非p53依賴途徑誘導產生。各蛋白表現相關性方面，p53及PCNA之標記指數於齒源性角化囊腫、含齒囊腫及根尖囊腫皆有明顯正相關（P＜0.0001、P＜0.05及P＜0.0001），因此推測可能有部分p53發生失活現象，導致細胞增殖發生。另外p21與MDM2及p21與PCNA於齒源性角化囊腫的表現也有明顯正相關（P＜0.0001及P＜0.01）。
齒源性角化囊腫之p53及PCNA過度表現，及p53、p21、MDM2和PCNA陽性反應細胞於內襯上皮中獨特的分布模式，顯示出齒源性角化囊腫之內襯上皮細胞在增殖及分化的過程，不同於含齒囊腫及根尖囊腫。

In this study, we used an immunohistochemical method to investigate the expression of p53, p21, MDM2, and PCNA in 55 odontogenic keratocysts (OKC), 35 dentigerous cysts (DC), and 34 of radicular cysts (RC).
The results showed that the positive stained cells of p53, p21, MDM2, and PCNA in the epithelial lining of OKCs distributed predominantly in the parabasal layer, compared to DCs and RCs. The mean labeling indices of p53, p21, MDM2, and PCNA in OKCs were 20.8±16.2, 15.3±12.1, 27.9±18.3, and 31.7±17.1. The mean labeling indices of p53, p21, MDM2, and PCNA in DCs were 13.4±12.9, 16.9±15.3, 20.8±15.7, and 24.5±20.4. The mean labeling indices of p53, p21, MDM2, and PCNA in RCs were 9.9±9.2, 10.4±7.6, 23.3±18.0, and 16.2±13.5. The mean labeling indices of p53 and PCNA in OKC lining epithelium were both significantly higher than those in DC and RC lining epithelium. The mean labeling index of p53 in mulitilocular OKCs was significantly lower than that in unilocular OKCs (P<0.05). In DCs, the mean labeling index of PCNA was associated with the inflammatory degree in the cyst wall (P<0.05). Higher mean labeling index was found in DCs with severe inflammation than those with mild or moderate inflammation. In RCs, the mean labeling index of p21 in RCs with intra-epithelial hyaline bodies was lower than that in RCs without intra-epithelial hyaline bodies (P<0.05). The other clinicopathological parameters of OKCs, DCs and RCs were not correlated with the mean labeling indices of p53, p21, MDM2, and PCNA.
High p53 staining rate was noted in OKCs, DCs, and RCs but the rare occurrence of p53+/p21-/MDM2- immunophenotype in OKCs, DCs and RCs suggests that there may be no mutation of p53 gene in OKCs, DCs, and RCs. presence of p21 and MDM2 was found in both p53+ and p53- OKCs, DCs, and RCs, indicating that the p21 and MDM2 proteins are produced through both p53-dependent and p53-independent pathways. Considering the interaction among p53, p21, MDM2, and PCNA, we found that the labeling index of p53 in OKC, DC and RC was positively correlated with that of PCNA in OKC, DC and RC (P<0.0001, P<0.05, P<0.0001). This suggests that some of p53 proteins are inactivated, resulting in occurrence of cell proliferation. In addition, the labeling index of p21 in OKC was also positively correlated with those of MDM2 and PCNA in OKC (P<0.0001 and P<0.01).
Our results suggest that the overexpression of p53 and PCNA in OKC and the unique distribution of p53, p21, MDM2, and PCNA positive cells within the lining epithelium of OKC reflect differences in proliferation and differentiation of the lining epithelial cells between OKC and DC or RC.

目錄
表目錄…………………………………………………………………………Ⅲ
圖目錄…………………………………………………………………………Ⅳ
第一章中文摘要…………………………………………………………1
第二章 英文摘要……………………………………………………………3
第三章前言………………………………………………………………5
一、研究動機…………………………………………………………5
二、研究目的…………………………………………………………6
第四章文獻回顧…………………………………………………………7
一、 齒源性角化囊腫……………………………………………………7
二、 含齒囊腫……………………………………………………………12
三、 根尖囊腫……………………………………………………………14
四、 p53蛋白………………………………………………………………15
五、 p21蛋白………………………………………………………………20
六、 MDM2蛋白……………………………………………………………23
七、 PCNA…………………………………………………………………25
第五章材料與方法………………………………………………………27
一、標本取樣…………………………………………………………27
二、標本之固定與包埋………………………………………………27
三、實驗方法…………………………………………………………27
第六章結果………………………………………………………………34
一、齒源性角化囊腫、含齒囊腫及根尖囊腫之臨床與病理學發現 ………………………………………………………………………………34
二、齒源性角化囊腫、含齒囊腫及根尖囊腫之p53、p21、MDM2及PCNA抗原染色結果及相互比較……………………………………………37
三、齒源性角化囊腫、含齒囊腫及根尖囊腫間p53、p21、MDM2及PCNA抗原染色結果表現差異………………………………………………40
四、齒源性角化囊腫、含齒囊腫及根尖囊腫之p53、p21、MDM2及PCNA抗原染色結果及其和不同臨床病理參數之相關性…………………41
五、齒源性角化囊腫、含齒囊腫及根尖囊腫合併p53、p21及MDM2抗原染色結果…………………………………………………………………45
六、齒源性角化囊腫、含齒囊腫及根尖囊腫之p53、p21、MDM2及PCNA抗原間表現相關性……………………………………………………46
七、p53陽性與p53陰性齒源性角化囊腫、含齒囊腫及根尖囊腫之p21、MDM2及PCNA平均標記指數及其差異………………………………47
第七章討論……………………………………………………………49
一、p53蛋白免疫組織化學染色於齒源性角化囊腫、含齒囊腫及根尖囊腫的表現………………………………………………………………49
二、p21蛋白免疫組織化學染色於齒源性角化囊腫、含齒囊腫及根尖囊腫的表現………………………………………………………………50
三、MDM2蛋白免疫組織化學染色於齒源性角化囊腫、含齒囊腫及根尖囊腫的表現………………………………………………………………50
四、PCNA蛋白免疫組織化學染色於齒源性角化囊腫、含齒囊腫及根尖囊腫的表現………………………………………………………………51
五、齒源性角化囊腫、含齒囊腫及根尖囊腫臨床與組織病理參數和p53、p21、MDM2及PCNA標記指數的相關性………………………………52
六、p53、p21、MDM2及PCNA標記指數間之相關性…………………53
第八章結論………………………………………………………………56
附表與附圖…………………………………………………………………59
參考文獻………………………………………………………………………74

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