本文選題：腎透明細(xì)胞癌 + 腎細(xì)胞癌��； 參考：《天津醫(yī)科大學(xué)》2014年碩士論文

【摘要】：目的 腎細(xì)胞癌(renal cell carcinoma, RCC)是泌尿生殖系統(tǒng)中最常見的惡性腫瘤之一,發(fā)病率占全身惡性腫瘤的3%,僅次于膀朧癌,居泌尿系腫瘤第二位。由于缺乏早期診斷標(biāo)志,導(dǎo)致腎癌患者高比例的腫瘤轉(zhuǎn)移,其中位生存期約為13個月,在腎細(xì)胞癌的診斷和治療上有待于尋找新的作用靶點。在腎細(xì)胞癌中,腎透明細(xì)胞癌(clear cell renal cell carcinoma, CCRCC)類型約占65%-80%。 腫瘤的發(fā)生是在基因和基因水平上多步驟、多因素的過程,最終導(dǎo)致不可控制的細(xì)胞增殖、轉(zhuǎn)化和死亡。蛋白質(zhì)序列中的絲氨酸/蘇氨酸-脯氨酰鍵的磷酸化,是控制細(xì)胞周期循環(huán)、調(diào)節(jié)細(xì)胞增殖和分化的關(guān)鍵性信號調(diào)節(jié)機制。Pinl是肽基脯氨酰異構(gòu)酶家族成員之一,它能使蛋白質(zhì)中磷酸化的絲氨酸/蘇氨酸-脯氨酰鍵異構(gòu)化,由順式變?yōu)榉词?調(diào)節(jié)磷酸化蛋白質(zhì)活性。Pinl的過表達可能參與了多種腫瘤的發(fā)生發(fā)展。CyclinD1是G1/S轉(zhuǎn)換的限速控制因素,抑制CyclinD1的活性,可以使細(xì)胞受阻于G1期,限制瘤細(xì)胞的增殖,從而抑制腫瘤生長。研究發(fā)現(xiàn),CyclinD1在多種腫瘤中過表達。 本研究采用免疫組化法檢測Pinl與CyclinD1蛋白在腎透明細(xì)胞癌及癌旁腎臟組織中的表達情況及它們之間的相關(guān)性,探討其在腎透明細(xì)胞癌中的作用。 材料與方法 本研究所使用病例取自天津泌尿外科研究所、天津醫(yī)科大學(xué)第二醫(yī)院泌尿外科2007年6月～2009年1月手術(shù)切除腎透明細(xì)胞癌組織標(biāo)本且臨床資料齊備者102例。男64例,女38例；年齡30-81歲,平均56歲。按照WHO分級標(biāo)準(zhǔn),G133例,G247例,G322例。采用ACJJ分期,Ⅰ期44例,Ⅱ期28例,Ⅲ期24例,Ⅳ期6例。另取腫瘤旁2cm區(qū)域的腎組織70例,作為對照組。所有染色切片均由兩位富有經(jīng)驗的病理醫(yī)生在同一條件下用光學(xué)顯微鏡采用雙盲法閱片。 用免疫組化SP法檢測Pinl和CyclinD1的表達。結(jié)果判定：Pinl蛋白表達定位于細(xì)胞漿和(或)細(xì)胞核。根據(jù)其染色強度計分：無染色為0,淡紅色為1,紅色為2,橘紅色為3；按染色陽性細(xì)胞百分率計分：陽性細(xì)胞百分率25%者為0,陽性細(xì)胞百分率25%-49%者為1,陽性細(xì)胞百分率50%-74%者為2,≥75%者為3。最后判斷標(biāo)準(zhǔn)為上述兩項得分相乘,得分≥3分為過度表達。CyclinD1蛋白表達定位于細(xì)胞核和(或)細(xì)胞漿,陽性細(xì)胞率小于10%為陰性(-),陽性細(xì)胞率大于等于10%為陽性(+)。 對本研究中102例患者進行術(shù)后隨訪,隨訪其術(shù)后遠(yuǎn)處轉(zhuǎn)移、局部復(fù)發(fā)、5年生存率等指標(biāo),隨訪時間為2011年6月～2014年2月。應(yīng)用SPSS12.0醫(yī)學(xué)統(tǒng)計軟件,對Pinl和CyclinD1的表達與臨床病理特征的關(guān)系用卡方檢驗,P0.05為有統(tǒng)計學(xué)意義。 結(jié)果 1.Pinl和CyclinD1在腎透明細(xì)胞癌組織中的表達 在癌旁組織中,Pinl蛋白的過表達率為11.43%；在腎透明細(xì)胞癌組織中,Pinl蛋白的過表達率為68.63%,在腎癌組織中Pinl的表達強度顯著高于癌旁正常腎臟組織。腎癌組織中的過表達率比癌旁組織明顯升高,兩組間比較顯示差異有統(tǒng)計學(xué)意義(P0.01)。 CyclinD1的表達主要位于細(xì)胞核,強陽性時胞漿尚有表達。本研究顯示,CyclinD1在癌旁組織中僅有極少量陽性表達,大多數(shù)呈不表達。CyclinD1在腎透明細(xì)胞癌中的表達率為62.75%,明顯高于癌旁組織的表達率8.57%。兩組間比較有統(tǒng)計學(xué)差異(P0.01)。 2.Pinl和CyclinD1在腎透明細(xì)胞癌中的表達與臨床病理特征的關(guān)系 Pinl的過表達與患者年齡、性別、腫瘤大小、病理分級等參數(shù)無顯著相關(guān),與臨床分期呈正相關(guān)(P0.05)。CyclinD1的表達與臨床分期也呈正相關(guān)(P0.05),而與患者的年齡、性別、病理分級等參數(shù)無顯著相關(guān)。 關(guān)于患者術(shù)后隨訪情況,102例腎透明細(xì)胞癌患者均獲隨訪。所有患者均術(shù)后隨訪5年,其中有2例患者失訪,2例因其他疾病和意外死亡而不計入隨訪樣本量,對余下98例患者進行隨訪統(tǒng)計。根據(jù)統(tǒng)計結(jié)果,Pinl的過表達及cyclinD1的表達與患者遠(yuǎn)期復(fù)發(fā)率和5年存活率等參數(shù)并無顯著相關(guān)(P0.05)。 3.腎透明細(xì)胞癌中Pinl和CyclinD1表達的相關(guān)性 在Pinl過表達的70例腎透明細(xì)胞癌中,50例的CyclinD1呈現(xiàn)陽性表達,Pinl低表達的32例腎透明細(xì)胞癌中,有18例的CyclinD1蛋白呈陰性,二者在腎透明細(xì)胞癌中的表達呈顯著正相關(guān)(P0.01)。 結(jié)論 1.Pinl在腎透明細(xì)胞癌組織中的表達明顯高于癌旁腎臟組織。CyclinD1在腎透明細(xì)胞癌組織中的表達明顯高于癌旁腎臟組織。 2.Pinl的過表達與腎透明細(xì)胞患者的年齡、性別、腫瘤大小、病理分級等無顯著相關(guān),與臨床分期呈正相關(guān)。CyclinD1的表達與年齡、性別、組織類型、病理分級等無顯著相關(guān),與臨床分期呈正相關(guān)。 3.Pinl及CyclinD1與腎透明細(xì)胞癌患者的復(fù)發(fā)率、轉(zhuǎn)移率、生存率等預(yù)后參數(shù)無明顯相關(guān)。 4.Pinl與CyclinD1在腎透明細(xì)胞癌中的表達密切相關(guān),提示Pinl的過表達可能促進CyclinD1的表達,Pinl可能為CyclinD1的上層調(diào)控因素。Pinl和CyclinD1異常表達可能共同參與腎透明細(xì)胞癌的發(fā)生、發(fā)展。
[Abstract]:objective
Renal cell carcinoma (RCC) is one of the most common malignant tumors in the genitourinary system. The incidence is 3% of the malignant tumor of the whole body. It is second only to bladder cancer and is the second place in the urinary tumor. Due to the lack of early diagnosis, it leads to a high proportion of tumor metastases in the patients with renal cancer, with a survival time of about 13 months in renal cell carcinoma. The diagnosis and treatment of renal cell carcinoma (clear cell renal cell carcinoma, CCRCC) are about 65%-80%. in renal cell carcinoma.
The occurrence of tumor is the process of multistep and multiple factors at the gene and gene level, which eventually leads to the non controlled cell proliferation, transformation and death. The phosphorylation of serine / threonine prolyl key in the protein sequence is the key signal regulating mechanism for controlling cell cycle cycle, regulating cell proliferation and differentiation.Pinl is the peptide based proline One of the members of the family of aminoacyl isomerase, which can make the phosphorylated serine / prolyl isomerization of phosphorylated protein in the protein from cis to trans, regulating the overexpression of phosphorylated protein activity.Pinl may participate in the development of a variety of tumors and.CyclinD1 is the limiting factor of G1/S conversion and inhibits the activity of CyclinD1. Cells are blocked in phase G1, which limits the proliferation of tumor cells and thus inhibits tumor growth. It is found that CyclinD1 is overexpressed in many tumors.
In this study, the expression of Pinl and CyclinD1 protein in renal clear cell carcinoma and adjacent renal tissue and the correlation between them were detected by immunohistochemical method, and the role of them in renal clear cell carcinoma was investigated.
Materials and methods
The cases were taken from the Tianjin Department of Urology, Tianjin Department of Urology, Second Hospital Affiliated to Tianjin Medical University in June 2007 ~ January 2009 to excision the renal clear cell carcinoma tissue specimens and the clinical data of 102 cases. Male 64 cases, female 38 cases, age 30-81 years, mean 56 years. According to WHO grading standard, G133 cases, G247 cases, G322 cases. AC JJ staging, 44 cases in stage I, 28 cases in stage II, 24 in stage III and 6 in stage IV. 70 cases of renal tissue in the 2cm region beside the tumor were taken as the control group. All the stained sections were used by two rich experienced pathologists on the same condition with the optical microscope to read the double blind method.
The expression of Pinl and CyclinD1 was detected by immunohistochemical SP. Results: the expression of Pinl protein was located in cytoplasm and (or) nuclei. According to its staining strength, no staining was 0, light red was 1, red was 2, orange red was 3, positive cells percentage was 0, positive cell percentage was 0, positive cell percentage was 25%- The percentage of positive cells was 1, the percentage of positive cell percentage 50%-74% was 2, the final judgment of 75% was 3., and the score was more than 3. The expression of over expression of.CyclinD1 protein was located in the nucleus and (or) cytoplasm, the positive cell rate was less than 10% as negative (-), the positive cell rate was more than 10% as positive (+).
In this study, 102 patients were followed up after operation, followed up with distant metastasis, local recurrence, 5 year survival rate and so on. The follow-up time was from June 2011 to February 2014. The relationship between the expression of Pinl and CyclinD1 and the clinicopathological features was checked with chi square, and P0.05 was statistically significant.
Result
Expression of 1.Pinl and CyclinD1 in renal clear cell carcinoma
In the para cancerous tissue, the overexpression of Pinl protein was 11.43%, and the overexpression rate of Pinl protein was 68.63% in the renal clear cell carcinoma tissue. The expression of Pinl in the renal carcinoma tissue was significantly higher than that in the normal renal tissue adjacent to the carcinoma. The overexpression rate in the renal carcinoma tissue was significantly higher than that in the para cancerous tissue. The difference between the two groups showed a significant difference. (P0.01).
The expression of CyclinD1 was mainly located in the nucleus and strongly positive cytoplasm was still expressed. This study showed that only a few positive expressions of CyclinD1 were found in the para cancerous tissues, and the expression rate of most of the non expression.CyclinD1 in the renal clear cell carcinoma was 62.75%, which was significantly higher than that of the para cancerous tissue 8.57%. two groups (P0.01).
Expression of 2.Pinl and CyclinD1 in clear cell renal cell carcinoma and their relationship with clinicopathological characteristics
There was no significant correlation between the overexpression of Pinl and the patient's age, sex, tumor size and pathological classification, and positive correlation with clinical stages (P0.05).CyclinD1 expression was also positively correlated with clinical stage (P0.05), but had no significant correlation with age, sex, pathological classification and other parameters.
102 cases of renal clear cell carcinoma were followed up for 5 years. All patients were followed up for 5 years, of which 2 cases were lost, 2 were followed up with other diseases and accidental deaths, and the remaining 98 patients were followed up. According to the statistical results, the expression of Pinl and the expression of cyclinD1 and patients There was no significant correlation between long-term recurrence rate and 5 year survival rate (P0.05).
Correlation between Pinl and CyclinD1 expression in 3. renal clear cell carcinoma
Of the 70 cases of Pinl overexpression of renal clear cell carcinoma, 50 cases of CyclinD1 showed positive expression. Of the 32 cases of renal clear cell carcinoma with low expression of Pinl, 18 cases of CyclinD1 protein were negative. The expression of the two in the renal clear cell carcinoma was significantly positive correlation (P0.01).
conclusion
The expression of 1.Pinl in the tissues of renal clear cell carcinoma was significantly higher than that in the paracancerous renal tissue. The expression of.CyclinD1 in the renal clear cell carcinoma tissue was significantly higher than that in the para cancerous renal tissue.
There was no significant correlation between the overexpression of 2.Pinl and the age, sex, tumor size and pathological grade of the patients with renal transparent cells. There was no significant correlation between the expression of.CyclinD1 and the age, sex, type of tissue, pathological grade and so on, which was positively correlated with the clinical stage.
3.Pinl and CyclinD1 were not correlated with the recurrence rate, metastasis rate, survival rate and other prognostic parameters of patients with clear cell renal cell carcinoma.
The expression of 4.Pinl and CyclinD1 is closely related to the expression of renal clear cell carcinoma, suggesting that the overexpression of Pinl may promote the expression of CyclinD1. Pinl may be the upper regulatory factor of CyclinD1, the abnormal expression of.Pinl and CyclinD1 may participate in the occurrence and development of renal clear cell carcinoma.
【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R737.11

【參考文獻】

相關(guān)期刊論文 前10條

1 徐洪濤,王恩華;E鈣粘蛋白-環(huán)連蛋白復(fù)合體與腫瘤[J];國外醫(yī)學(xué)(腫瘤學(xué)分冊);2004年02期

2 敖然;王穎;張道榮;;Pin1與CyclinD1在肝癌中的表達及意義[J];山西醫(yī)藥雜志;2009年10期

3 張軍暉,王曉峰,葉海云,王瑞珩,虞有智;p27kipl和cyclin D1在腎細(xì)胞癌中的表達及生物學(xué)意義[J];中華泌尿外科雜志;2001年05期

4 于君,斯蒂芬.米爾可,丹尼爾.斯可地,溫福尼格,埃寧格爾,愛可哈德.拜爾道夫,馬蒂爾斯.易博特,比特.馬福泰尼;Cyclin基因在胃癌患者及其第一代親屬中的表達(英文)[J];Chinese Medical Journal;2002年05期

5 趙曉榮,鄧琳,翁新憲,顧煥華,鄧錫云,曹亞;周期蛋白D1在鼻咽癌細(xì)胞系中功能及意義的深入研究[J];中華腫瘤雜志;2001年05期

6 林美舉;吳河水;張景輝;張磊;徐建波;;Pin1和周期素D1在胰腺癌中的表達及其意義[J];中國普通外科雜志;2007年05期

7 馬波;趙吉生;丁大勇;;利用蛋白質(zhì)組技術(shù)進行胃癌差異蛋白質(zhì)研究[J];中華胃腸外科雜志;2006年06期

8 ;Expression of Egr-1,c-fos and cyclin D1 in esophageal cancer and its precursors:An immunohistochernical and in situ hybridization study[J];World Journal of Gastroenterology;2004年04期

9 Chang-Jae Kim;Yong-Gu Cho;Yong-Gyu Park;Suk-Woo Nam;Su-Young Kim;Sug-Hyung Lee;Nam-Jin Yoo;Jung-Young Lee;Won-Sang Park;Young-Mok Yang;;Pin1 overexpression in colorectal cancer and its correlation with aberrant β-catenin expression[J];World Journal of Gastroenterology;2005年32期

10 ;Effects of ischemic preconditioning on cyclinD1 expression during early ischemic reperfusion in rats[J];World Journal of Gastroenterology;2006年18期

，

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