Expression of p53, inducible nitric oxide synthase and vascular endothelial growth factor in gastric precancerous and cancerous lesions: correlation with clinical features
Expression of p53, inducible nitric oxide synthase and vascular endothelial growth factor in gastric precancerous and cancerous lesions: correlation with clinical features
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DOI：
10.1186/1471-2407-2-8
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发表时间：
2002-04-29
期刊：
影响因子：
3.8
通讯作者：
Xie, XJ
中科院分区：
文献类型：
--
作者：
Feng, CW;Wang, LD;Xie, XJ
背景：肿瘤的生长和转移取决于通过血管生成提供充足的血液供应。最近的研究表明，诱导型一氧化氮合酶 (iNOS)、血管内皮生长因子 (VEGF) 和肿瘤抑制因子 p53 是血管生成过程的基本作用标记。 iNOS 和 VEGF 的过度表达已被证明可诱导肿瘤中的血管生成。 P53 通过下调 VEGF 和 iNOS 抑制血管生成。然而，胃癌发生过程中p53、VEGF、iNOS的表达与临床特征的相关性尚未得到很好的表征。方法：采用免疫组化（抗生物素蛋白-生物素-过氧化物酶复合物法）对随机选取的55例胃癌患者和60例胃癌高发区群众调查的无症状受试者，采用免疫组织化学法测定胃癌癌前病变和癌变中p53、iNOS和VEGF的表达及其与临床特征的关系。结果：胃癌中p53、iNOS和VEGF免疫染色阳性率分别为51%、44%和51%，与TNM分期相关，但GC在不同胃壁浸润深度的组间差异无统计学意义。 iNOS 蛋白免疫染色阳性反应与淋巴结转移显着相关（p = 0.019；Spearman 相关系数）。低分化胃癌中P53蛋白的积累高于高分化胃癌。在胃活检中，在组织学正常组织和慢性浅表性胃炎（CSG）中未观察到 p53、iNOS 和 VEGF 阳性免疫染色。而慢性萎缩性胃炎（CAG）、肠化生（IM）和不典型增生（DYS）不同病变严重程度的组织中均可见p53、iNOS和VEGF免疫染色阳性，且阳性率随着病变从CAG→IM→DYS的进展而增加。在无症状受试者的 CAG、IM 和 DYS 活检样本以及 GC 患者的胃癌组织中，p53、iNOS 和 VEGF 免疫染色的同时阳性和阴性率较高。结论：本研究结果表明，p53 蛋白积累以及 iNOS 和 VEGF 表达增加可能是胃癌发生和肿瘤侵袭性的原因。
Background: The growth and metastasis of tumors depend on the development of an adequate blood supply via angiogenesis. Recent studies indicate that the inducible nitric oxide synthase ( iNOS), vascular endothelial growth factor (VEGF) and the tumor suppressor p53 are fundamental play-markers of the angiogenic process. Overexpression of iNOS and VEGF has been shown to induce angiogenesis in tumors. P53 suppresses angiogenesis by down-regulating VEGF and iNOS. The correlation of expression of p53, VEGF and iNOS and clinical features in gastric carcinogenesis, however, has not been well characterized.Methods: The expression of p53, iNOS and VEGF in gastric precancerous and cancerous lesions and its relation with the clinical features was determined with immunohistochemistry (avidin-biotin-peroxidase complex method) on 55 randomly selected GC patients and 60 symptom-free subjects from the mass survey in the high-incidence area for GC in Henan, northern China.Results: The positive immunostainig rates for p53, iNOS and VEGF in gastric carcinomas were 51%, 44% and 51%, respectively, and correlated well with TNM stages, but did not show significant difference among the groups with different degrees of gastric wall invasion depth by GC. A positive immunostaining reaction for the iNOS protein was significantly correlated with lymph node metastasis (p = 0.019; Spearman correlation coefficient). P53 protein accumulation was higher in the poorly-differentiated gastric carcinoma than in well-differentiated one. In gastric biopsies, no positive immunosatining was observed for p53, iNOS and VEGF in the histologically normal tissue and chronic superficial gastritis (CSG). However, p53, iNOS and VEGF positive immunostaining was observed in the tissues with different severities of lesions of chronic atrophic gastritis (CAG), intestinal metaplasia (IM) and dysplasia (DYS), and the positive rates increased with the lesion progression from CAG to IM to DYS. A high coincidental positive and negative immunostaining rate for p53, iNOS and VEGF was observed both in biopsy samples with CAG, IM and DYS from the symptom-free subjects and in gastric cancer tissue from the GC patients.Conclusions: The present results indicated that p53 protein accumulation and increased expression of iNOS and VEGF might be responsible for gastric carcinogenesis and tumor aggressiveness of gastric cancer.