周祖述臺灣大學：臨床醫學研究所許永和Hsu, Yung-HoYung-HoHsu2007-11-272018-07-062007-11-272018-07-062006http://ntur.lib.ntu.edu.tw//handle/246246/55483背景：腎細胞癌源自於腎小管上皮且約佔所有成年人癌症之百分之三。遠端轉移是造成患者死亡之主要原因，然而目前尚無正確及可信之生物標記以供預測腎細胞癌患者其將來產生轉移之機率大小。Podocalyxin (PC)是一抗黏著分子，其功能在於使腎絲球足細胞能維持其開放之過濾隙，最近研究發現它與某些人類癌症之產生或惡化有關。所以我們著手研究PC是否能成為預測腎細胞癌轉移及預後之生物標記。 方法：我們從台大病理科及泌尿科總共獲得398個福馬林固定、石蠟包埋之腫瘤組織切塊，這些腎臟腫瘤蠟塊來自於西元1995年1月至2004年12月間在台大醫院因被診斷腎細胞癌而接受腎切除之患者。只有病人具備清楚可供研究之臨床及病理資料才被加入此一研究，總共有303位。我們以免疫組織化學方法評估PC此蛋白在不同病人腫瘤組織是否有過量表現，並且以電腦自動影像分析系統量化代表案例組織切片PC有無過量表現之差異，以驗證主觀判讀之正確性。並以病人之各種臨床病理資料為基本變異數，分析其在PC有無過量表現(陽性及陰性)兩組間之統計差異，再以單一變數及多變數分析PC表現及各危險因子對轉移或存活之影響。 結果：在303個腎細胞癌病人的腫瘤組織中，有29個(9.6%) PC蛋白陽性或過量表現。過量表現PC蛋白與腫瘤較高的細胞核分化分級有明顯之統計相關(p＜0.001)，類似的關係也在較後期的腫瘤分期可見到(p＝0.003)，至於癌症轉移的情形也較容易發生在PC蛋白表現陽性的病人(p＜0.001)。以Kaplan-Meier方法得到的存活曲線PC陽性顯然比PC陰性其無轉移存活期間明顯較短(p＜0.0001)，腎癌存活期間及總存活期間也顯著較短(p＜0.0001)。以Cox迴歸多變數分析腫瘤組織之PC蛋白表現(陽性對陰性)其無轉移存活期間之危害率為3.59 (95％信賴區間1.51~8.53，p=0.004)，而腎癌存活期間之危害率為7.46 (95％信賴區間2.51~22.22，p＜0.001)。 結論：對於腎細胞癌患者，其腫瘤組織若有PC過量表現之情形，則較容易發生遠端轉移、存活也較短，PC有可能成為腎細胞癌患者早發轉移及預後不良之預測因子。Background Renal cell carcinoma (RCC) arises from renal tubular epithelium and accounts for approximately 3% of adult malignancy. Distant metastasis is the main cause of mortality for this disease; however, no reliable biomarker available today is capable of predicting the chance of metastasis in afflicted RCC patients. Podocalyxin (PC), an anti-adhesion molecule that maintains an open filtration slit in podocytes of the renal glomerulae, has been recently implicated in the tumorigenesis and progression of a number of human cancers. We therefore set up to investigate whether PC can be a useful biomarker to predict metastasis and prognosis of RCC. Methods We obtained 398 paraffin-embedded tumor samples from RCC patients who had received nephrectomy between January 1995 and December 2004 in National Taiwan University Hospital. Totally 303 RCC patients with adequate clinical and pathological information were recruited into this study. We assessed PC expression status by immunohistochemistry (IHC) and computerized image analyzer for objective and quantitative analysis of IHC staining. Patient’s clinicopathological data, which were collected as baseline variables, were categorized into PC-negative and PC-positive subgroups. These clinical, pathological, and laboratory data were analyzed for their possible correlation to the outcome and survival of this cohort. Results Among 303 RCC tumor samples, 29 (9.6%) were PC-positive. Increasing PC expression was significantly associated with advanced grade tumors (p<0.001). Similar relationship was also observed in histological type of non-clear cell and clear cell type tumors (p=0.003), and metastasis found at surgery or during later follow-up to no metastasis patients (p<0.001). Kaplan-Meier analysis reveals that patients with PC-positive tumors have decreased metastasis-free survival (p<0.0001), disease-specific survival (p<0.0001) and overall survival (p<0.0001). Cox expression multivariable analysis of PC status (positive vs negative) in primary tumors showed hazard ratios of 3.59 (95% CI 1.51-8.53, p=0.004) for metastasis-free survival and 7.46 (95% CI 2.51-22.22, p<0.001) for disease-specific survival. Conclusions Podocalyxin over-expression is a poor prognostic predictor of renal cell carcinoma. It can serve as a useful biomarker to identify patients with increasing possibility of early metastasis and poor prognosis.一. 中文摘要…………………………………………………………………….1 二. 緒論………………………………………………………………………….2 三. 研究方法與材料…………………………………………………………….6 四. 結果………………………………………………………………………….9 五. 討論…………………………………………………………………………11 六. 展望…………………………………………………………………………13 七. 英文簡述……………………………………………………………………15 八. 參考文獻……………………………………………………………………17 九. 圖表…………………………………………………………………………191500711 bytesapplication/pdfen-US足萼素腎細胞癌轉移PodocalyxinRenal cell carcinomaMetastasis[SDGs]SDG3texthttp://ntur.lib.ntu.edu.tw/bitstream/246246/55483/1/ntu-95-P94421019-1.pdf