Kevans David, Foley Jane, Tenniswood Martin, Sheahan Kieran, Hyland John, O'Donoghue Diarmuid, Mulcahy Hugh, O'Sullivan Jacintha
Centre for Colorectal Disease, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland.
Cancer Epidemiol Biomarkers Prev. 2009 Feb;18(2):393-9. doi: 10.1158/1055-9965.EPI-08-0302. Epub 2009 Jan 20.
The role of clusterin in tumor growth and progression remains unclear. Overexpression of cytoplasmic clusterin has been studied in aggressive colon tumors; however, no correlation between clusterin expression and survival in colorectal cancer has been identified to date. We assessed levels of clusterin expression in a group of stage II colorectal cancer patients to assess its utility as a prognostic marker. The study included 251 patients with stage II colorectal cancer. Tissue microarrays were constructed and immunohistochemistry done and correlated with clinical features and long term outcome. Dual immunofluorescence and confocal microscopy were used with terminal deoxynucleotidyl-transferase-mediated dUTP nick-end labeling probes and clusterin antibody to assess the degree of co localization. Percentage epithelial cytoplasmic staining was higher in tumor compared with nonadjacent normal mucosa (P < 0.001). Within the stromal compartment, percentage cytoplamic staining and intensity was lower in tumor tissue compared with normal nonadjacent mucosa (P < or = 0.001). Survival was significantly associated with percentage epithelial cytoplasmic staining (P < 0.001), epithelial cytoplasmic staining intensity (P < 0.001), percentage stromal cytoplasmic staining (P = 0.002), and stromal cytoplasmic staining intensity (P < 0.001). Clusterin levels are associated with poor survival in stage II colorectal cancer.
聚集素在肿瘤生长和进展中的作用仍不清楚。在侵袭性结肠肿瘤中已对细胞质聚集素的过表达进行了研究；然而，迄今为止尚未发现聚集素表达与结直肠癌患者生存率之间存在相关性。我们评估了一组II期结直肠癌患者的聚集素表达水平，以评估其作为预后标志物的效用。该研究纳入了251例II期结直肠癌患者。构建了组织微阵列并进行了免疫组织化学检测，并将其与临床特征和长期预后相关联。使用双免疫荧光和共聚焦显微镜，结合末端脱氧核苷酸转移酶介导的dUTP缺口末端标记探针和聚集素抗体，以评估共定位程度。与非相邻正常黏膜相比，肿瘤中的上皮细胞质染色百分比更高（P < 0.001）。在间质区室中，与非相邻正常黏膜相比，肿瘤组织中的细胞质染色百分比和强度更低（P ≤ 0.001）。生存率与上皮细胞质染色百分比（P < 0.001）、上皮细胞质染色强度（P < 0.001）、间质细胞质染色百分比（P = 0.002）和间质细胞质染色强度（P < 0.001）显著相关。聚集素水平与II期结直肠癌患者的不良生存率相关。
