第三型核醣核酸內切酶Dicer在泌尿上皮癌免疫組織化學染色表現與臨床病理結果之關聯

Association of Immunohistochemical Expression of RNase III endoribonuclease-Dicer and Clinicopathological Outcome in Urothelial Carcinoma

王紹全(Shao-Chuan Wang)

指導教授 ： 林隆堯 ； 張浤榮

中山醫學大學/醫學院/醫學研究所/碩士(2013年)

https://doi.org/10.6834/CSMU.2013.00090

摘要

研究目的：微小核糖核酸異常調控已被認為是膀胱及上泌尿道泌尿上皮癌生成過程中重要之表觀遺傳變異。Dicer這種第三型內核糖核酸酶家族蛋白在微小核糖核酸生源過程中佔有必要之調控功能。本研究旨在探討Dicer免疫組織化學染色表現是否與泌尿上皮癌臨床病理特徵及病患存活有關聯。
研究方法及資料：從2006年六月至2009年七月，在同一家醫學中心總共收錄42位診斷為泌尿道泌尿上皮癌患者，利用Dicer免疫組織化學染色方式檢驗包括腎盂、輸尿管及膀胱之泌尿上皮癌組織。利用回溯性分析病例記載方式研究Dicer免疫組織化學染色表現，包括染色強度及分布，與疾病臨床病理特徵之相關，同時我們亦探討Dicer免疫組織化學染色表現對疾病存活之影響。
研究結果：總共有39位泌尿上皮癌病患符合納入標準並接受研究分析，Cochran-Armitage趨勢檢測顯示分化程度較惡化的腫瘤組織有較高強度的Dicer免疫組織化學染色強度表現（P=0.631），但未達統計上意義。唯一與Dicer免疫組織化學染色強度表現有關的臨床病理變項是腫瘤位置(P=0.038)。在單變項存活分析中，發現組織型態(P=0.046)及Dicer免疫組織化學染色強度(P=0.026)對整體存活有顯著影響。此外，Kaplan-Meier存活圖亦顯示Dicer免疫組織化學染色強度低的病患整體存活優於染色強度高者。
結論與建議：由我們的研究得知，在泌尿上皮癌組織中，較高的Dicer免疫組織化學染色強度與較差的疾病狀態及存活有關。雖然目前並無相關的臨床證據或理由，但我們的資料顯示Dicer免疫組織化學染色強度與腫瘤位置有某種關聯，期待有更多相關的研究能讓我們了解泌尿上皮癌中，Dicer在微小核糖核酸生源機制、腫瘤成因調控、生化指標意義、甚至是藥物治療價值等面向之角色。

關鍵字

Dicer ； 免疫組織化學染色 ； 微小核糖核酸 ； 第三型內核糖

並列摘要

Objective: Deregulation of microRNA have been proposed as one of the most important epigenetic alterations in urothelial carcinogenesis of bladder and upper urinary tract. Dicer, a RNase III endoribonuclease, is an essential regulator in microRNA biogenesis. The objective of this study is to investigate whether immunohistochemical expression of Dicer in urothelial carcinoma associates with conventional clinicopathological features and patient survival .
Methods and Materials: From June 2006 to July 2009, immunohistochemincal staining for Dicer was performed on tissues of upper urinary tract, including renal pelvis and ureter, and urinary bladder from 42 patients with primary urothelial carcinoma in a single medical center. Retrospective chart review of patient’s clinicaopathological characteristics was performed then correlated with the expression of Dice, including IHC intensity and distribution. We also investigated the impact of Dicer expression to overall survival.
Results: A total of 39 patients met the inclusion criteria and were included in the study. There was an increasing trend in proportions of high tumor grade across IHC intensity without statistical significance (Cochran-Armitage trend test, P=0.631). Tumor location was the only clinicopathological variant associated with Dicer IHC intensity (P=0.038). In univariant survival analysis, histological pattern (P=0.046) and Dicer IHC intensity (P=0.026) showed significant impact to overall survival. Besides, Kaplan-Meier plots also revealed the survival difference by high and low Dicer IHC intensity.
Conclusion and Suggestion: High Dicer IHC intensity expression is linked to poor disease state and decreased overall survival in urothelial carcinoma. Although there are no clinical evidences or rationale available currently, our data revealed association between Dicer IHC intensity and tumor location. Further studies is needed to understand the role of Dicer in aspects of microRNA machinery, carcinogenesis modulation, biochemical significance, and even therapeutic value in urothelial carcinoma of urinary tract.

並列關鍵字

Dicer ； immunohistochemical stain ； microRNA

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