p53基因突变与Wegener肉芽肿患者肾组织中肉芽肿形成的联系

p53 mutation associated with the renal granuloma formation in patients with Wegeners granulomatosis

目的 :探讨p5 3突变在Wegener肉芽肿 (WG)患者肾组织肉芽肿病变形成中的作用。 方法 :应用特异性抗体和免疫组织化学染色方法 ,对 6例WG患者及 6例其它原因致肾间质肉芽肿样病变的非WG患者的肾活检标本突变型p5 3进行了染色观察。 结果 :6例WG患者中 3例肾间质可见肉芽肿样病变 ,其肉芽肿样病变中央区细胞突变型p5 3染色阳性。在这一区域增殖细胞核抗原 (PCNA)亦呈强阳性。另 3例间质无肉芽肿样病变的WG患者 ,肾间质炎细胞浸润区和 6例非WG患者肾间质肉芽肿样病变区 ,突变型p5 3和PCNA染色均为阴性。所有患者肾小球及肾小管突变型p5 3染色均为阴性。 结论 :p5 3突变在WG的肉芽肿病变形成中起一定作用。突变型p5 3检测 ,可能为WG患者的诊断及伴肾间质肉芽肿样病变疾病的鉴别诊断提供新的途径。

Objective:Wegeners granulomatosis (WG)was reported closely associated with renal carcinoma.p53 mutation is one of the most common genetic abnormalities in malignancy.In present study we intended to explore the role of p53 mutation in renal granuloma formation in patients with WG. Methodology:Immunohistochemistry methods was used to detect the mutant p53 protein and proliferating cell nuclear antigen(PCNA)expression in the kidneys of 6 WG patients and 6 non WG patients with granulomatous interstitial nephritis by using specific anti mutant p53 antibody and anti PCNA antibody.Multiple immunolabelling technique was applied to identify the constituents of the renal granuloma in WG patients utilizing anti CD3 and anti CD20 antibody.Sera from 6 WG patients were subjected to screening for antineutrophil cytoplasm antibody(ANCA)by using indirect immunofluorescence method and enzyme linked immunosorbent assay. Results:In 3 out of 6 specimens of WG patients with renal interstitial granulomatous change,positive mutant p53 staining cells appeared in the central area of granuloma.Mutant p53 positive cells were also demonstrated positively by PCNA and CD20 staining.While in the other 3 cases of WG without granuloma,mutant p53 and PCNA staining were both negative,as well as in the granulomatous area in 6 non WG patients. Conclusion:p53 mutation may play a role in the process of granuloma formation in WG and can conceivably be used as a marker for the differential diagnosis in patients with renal granulomatous diseases.It is also served as an indicator for predicting the prognosis.