2016-08-012024-05-14https://scholars.lib.ntu.edu.tw/handle/123456789/658537摘要：泌尿上皮癌可能源自於整個泌尿道，包含從腎臟到尿道。大部分的泌尿上皮癌發生在膀胱（簡稱膀胱癌），只有5-10%發生在腎臟或輸尿管，稱之為上泌尿道泌尿上皮癌。膀胱癌的致病機轉根據基因突變可分為兩種：TP53 突變和FGFR3 突變。TP53突變常出現於侵襲性或高危險的膀胱癌，而FGFR3 突變較常發生在低惡性度的膀胱癌。雖然上泌尿道泌尿上皮癌和膀胱癌有著相同的病理學特徵，但上泌尿道泌尿上皮癌有著比較容易快速惡化的臨床過程。因為上泌尿道泌尿上皮癌較不常見，所以膀胱癌中關於TP53 和FGFR3 的研究就延續至上泌尿道泌尿上皮癌。研究發現，有著TP53突變的上泌尿道泌尿上皮癌預後較差，而含有FGFR3 突變的則有較好的存活率。這些基因突變的資料因為需取得足夠的檢體，在臨床應用上受到限制。氟18 去氧葡萄糖正子造影（簡稱正子造影）是一種廣泛應用於癌症診斷的影像技術。許多研究顯示具有KRAS 突變的非小細胞肺癌病患有著較高的正子造影攝取，這代表正子造影可以是預測基因突變的先驅檢驗。在膀胱癌中，具有TP53 突變的病人對於含鉑金類的化學治療藥物有較佳效果，而具有FGFR3 突變的反而對於針對FGFR3 的標把藥物沒有明顯療效。本研究將分析上泌尿道泌尿上皮癌的腫瘤在正子造影上的各種參數，以及與TP53 和FGFR3 突變的相關性，藉此預測腫瘤的惡性程度以及提供治療方向的依據。<br> Abstract: Urothelial carcinoma is derived from urothelium along the urinary tract from the renalpelvis to the urethra. The majority of urothelial carcinomas occurs in urinary bladder, withonly 5-10% in the ureter or renal pelvis, which is defined as upper tract urothelial carcinoma(UTUC). Pathogenesis pathways of bladder cancer have been widely studied which is dividedinto two groups: TP53 mutation and FGFR3 mutation. TP53 mutations are commonly seen inmuscle-invasive bladder cancer or high risk malignancy, while FGFR3 mutations are highlyprevalent in low-grade tumors. Although sharing with identical histopathological appearancewith bladder cancer, UTUCs have a more aggressive clinical course and poorer prognosis dueto lack of effective approaches for early detection. Findings of TP53 and FGFR3 mutations inbladder cancer were extrapolated into UTUC due to rarity of the disease, which revealed thatUTUCs with TP53 mutation were associated with poor prognosis and those with FGFR3mutation had better overall survival. However, the use of these molecular biomarkers beforetreatment is often limited due to difficulty in obtaining sufficient specimen. Positron emissiontomography (PET) using 18F-fluorodeoxyglucose (FDG) is a molecule imaging technique andhas been widely applied in oncology field. Studies have shown that Non-small-cell lungcancer patients with tumors harboring KRAS mutations showed significantly higher FDGuptake than wild-type patients, which indicated that FDG-PET/CT is a surrogate of molecular共2 頁 第2 頁表 CM02biomarkers and has potential roles choosing suitable patients for corresponding target therapy.It is proved that bladder cancer harboring TP53 mutations beneficially response tocisplatin-containing adjuvant chemotherapy but patients with FGFR3 mutations did not havegood response to tyrosine kinase inhibitor that binds to FGFR3. In this study, we aim toanalysis the uptake pattern of FDG-PET/CT in the primary tumor of UTUC and itsrelationship with mutations of TP53 and FGFR3, which may be benefit for clarifying tumoraggressiveness and possible role in connection with target therapy.