【摘要】：背景 腎細(xì)胞癌（Renal cell carcinoma，RCC），是泌尿系統(tǒng)常見的惡性腫瘤。外科切除器官局限性腫瘤為腎癌提供了一個(gè)治愈的機(jī)會，但接受手術(shù)治療的患者中約30％將發(fā)生遠(yuǎn)處轉(zhuǎn)移。RCC對放療化療均不敏感，而且免疫生物療法僅在一小部分病例上觀察到部分或完全緩解[1,2,3]。目前，腎癌發(fā)病的確切機(jī)制尚不明確，抑癌基因的失活和癌基因的激活可能發(fā)揮重要作用[4]，相關(guān)基因產(chǎn)物的檢測對腎癌的早期診斷具有重要的臨床意義。Tiam1是鳥苷酸轉(zhuǎn)換因子(guanine nucleotideexchange factors，GEFs)家族成員，參與到包括腎癌在內(nèi)的許多腫瘤的發(fā)生和轉(zhuǎn)移過程[5]。研究還發(fā)現(xiàn)Tiam1通過與CD44黏附分子相互作用可提高Rac1信號途徑和以透明質(zhì)酸（CD44的受體）的中介或基質(zhì)金屬蛋白酶的中介可促進(jìn)乳腺癌、結(jié)腸癌等瘤細(xì)胞侵潤及遷移[6,7,8]。因此，Tiam1聯(lián)合CD44表達(dá)更有助于反映細(xì)胞的侵襲及轉(zhuǎn)移狀態(tài)。目的 研究Tiam1、CD44在腎細(xì)胞癌組織中的表達(dá)情況，探討Tiam1、CD44在腎細(xì)胞癌發(fā)生、發(fā)展中的作用及其相互關(guān)系，以期對腎細(xì)胞癌的臨床診斷、治療和預(yù)后提供幫助。方法 應(yīng)用免疫組化方法（S-P法）檢測92例臨床腎細(xì)胞癌組織和20例癌旁正常腎組織中Tiam1、CD44的表達(dá)情況及其相互關(guān)系，并與腫瘤臨床分期、病理分級進(jìn)行等臨床特征進(jìn)行相關(guān)性分析。 結(jié)果 1.腎透明細(xì)胞癌組織中Tiam l蛋白陽性表達(dá)率為75%（69/92）,陽性表現(xiàn)為鏡下黃色或棕色細(xì)顆粒，以細(xì)胞質(zhì)中表達(dá)為主，其表達(dá)與腫瘤的臨床分期、有無淋巴結(jié)轉(zhuǎn)移及遠(yuǎn)處轉(zhuǎn)移有關(guān)，差異有統(tǒng)計(jì)學(xué)意義（P＜0.05）。其表達(dá)與腫瘤大小、年齡、性別無統(tǒng)計(jì)學(xué)意義(P＞0.05)；對照組的20例正常組織中Tiam1表達(dá)水平低，其表達(dá)率為15%（3/20）。 2. CD44在腎透明細(xì)胞癌組織中表達(dá)率為66.3%（61/92），位于細(xì)胞膜，陽性表現(xiàn)為鏡下褐色細(xì)顆粒，，其表達(dá)強(qiáng)度與臨床病理資料中Tiam1表達(dá)相符。對照組的20例正常組織中CD44表達(dá)水平低，其表達(dá)率為20%（4/20）。 3.經(jīng)統(tǒng)計(jì)學(xué)分析，兩者在腎癌組織中的表達(dá)呈正相關(guān)（相關(guān)系數(shù)r=0.315，χ2=10.14，P0.01）。 結(jié)論 1．腎透明細(xì)胞癌組織的Tiam1及CD44表達(dá)的水平皆與臨床分期以及有無淋巴結(jié)轉(zhuǎn)移和血管侵潤等密切相關(guān)，但與患者的年齡、性別，腫瘤大小等無關(guān)。 2．腎透明細(xì)胞癌組織的Tiaml及CD44的表達(dá)水平呈正相關(guān)，提示Tiam1與CD44二者的表達(dá)在腎細(xì)胞癌中可有協(xié)同作用，共同促使腫瘤在局部侵襲和淋巴結(jié)轉(zhuǎn)移。
[Abstract]:Background Renal cell carcinoma (Renal cell carcinoma,RCC) is a common malignant tumor of urinary system. Surgical resection of localized tumors of the organs provides an opportunity to cure renal cell carcinoma, but about 30% of the patients undergoing surgical treatment will have distant metastasis. RCC is not sensitive to radiotherapy and chemotherapy. And immunobiotherapy observed partial or complete remission in only a small number of cases [1, 2, 3]. At present, the exact mechanism of renal cell carcinoma is not clear, the inactivation of tumor inhibitor gene and the activation of tumor gene may play an important role [4]. The detection of related gene products is of great clinical significance for the early diagnosis of renal cell carcinoma. Tiam1 is a member of the guanylate conversion factor (guanine nucleotideexchange factors,GEFs family and is involved in the occurrence and metastasis of many tumors, including renal cell carcinoma [5]. It was also found that Tiam1 could enhance the Rac1 signal pathway by interacting with CD44 adhesion molecules and promoted the invasion and migration of breast cancer and colon cancer cells mediated by hyaluronic acid (CD44 receptor) or matrix metalloproteinases [6, 7, 8]. Therefore, the expression of Tiam1 combined with CD44 is more helpful to reflect the invasion and metastasis of cells. Objective to study the expression of Tiam1,CD44 in renal cell carcinoma (RCC) and to explore the role of Tiam1,CD44 in the occurrence and development of RCC and its relationship with each other, so as to provide help for clinical diagnosis, treatment and prognosis of RCC. Methods Immunohistochemical method (S 鈮

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