Oncogenic role of clusterin overexpression in multistage colorectal tumorigenesis and progression

AIM: To investigate the expression pattern of clusterin in colorectal adenoma-carcinoma-metastasis series, and to explore the potential role of dusterin in multistage colorectal tumorigenesis and progression.METHOD:S: A colorectal carcinoma (CRC)-tissue microarray (TMA), which contained 85 advanced CRCs including 43 cases of Dukes B, 21 of Dukes C and 21 of Dukes D tumors, were used for assessing the expression of clusterin (clone 41D) and tumor cell apoptotic index (AI) by immunohistochemistry and TUNEL assay, respectively. Moreover the potential correlation of dusterin expression with the patient'sclinical-pathological features were also examined. RESULTS: The positive staining of clusterin in different colorectal tissues was primarily a cytoplasmic pattern. Cytoplasmic overexpression of clusterin was detected in none of the normal coloredal mucosa, 17% of the adenomas, 46% of the primary CRCs, and 57% of the CRC metastatic lesions. In addition, a significant positive correlation between overexpression of clusterin and advanced clinical (Dukes) stage was observed (P＜0.01). Overexpression of cytoplasmic clusterin in CRCs was inversely correlated with tumor apoptotic index (P＜0.01), indicating the anti apoptotic function of cytoplasmic clusterin in CRCs.CONCLUSION: These data suggests that overexpression of cytoplasmic dustin might be involved in the tumorigenesis and/or progression of CRCs. The anti-apoptotic function of cytoplasmic dusterin may be responsible, at least in part, for the development and biologically aggressive behavior of CRC.

VEGF、VEGF-C和VEGFR-3蛋白表达增加与前列腺癌进展期的相关性研究(英文)

目的:研究前列腺癌(PCa)组织及癌周正常组织中微血管密度(MVD)、血管内皮细胞生长因子(VEGF)、VEGF-C 及血管内皮细胞生长因子受体3(VEGFR-3)的表达差异,探讨 VEGF,VEGF-C 及 VEGFR-3蛋白的表达与 PCa 进展期的相关性。方法:采用 SABc 免疫组化染色法检测71例 PCa 患者的组织样本中 CD34、VEGF、VEGF-C 及 VEGFR-3的表达。结果:与癌周正常组织相比,PCa 上皮/肿瘤细胞内 VEGF、VEGF-C 及 VEGFR-3的表达均显著上调(P<0.01)。Jewett-Whitmore 分期的 D 期患者癌灶内 VEGF-C 和 VEGFR-3的表达均显著高于 A、B 或 C 期患者(P<0.01)。另外在 Jewett-Whitmore 分期与 VEGF-C 表达(r_s=0.738,P<0.01)、临床分期与 VEGFR-3(r_s=0.410,P<0.01)、VEGF-C 与 Gleason 评分(r_s=0.401,P<0.01)、VEGFR-3与 Gleason评分(r_s=0.581,P<0.001)、MVD 与 VEGF(r_s=0.492,P<0.001)之间均存在显著相关性。结论:VEGF、VEGF-C 和 VEGFR-3的表达增加与 PCa 的进展期密切相关。VEGF 促进肿瘤组织内部微血管密度增加,从而维持肿瘤组织的生长优势:而 VEGF-C 及 VEGFR-3的主要作用在于促进肿瘤组织淋巴管形成,进而促进癌细胞的转移。