Ikeguchi M, Sakatani T, Ueta T, Kaibara N
Department of Surgery I, Faculty of Medicine, Tottori University, Yonago, Japan.
J Cancer Res Clin Oncol. 2001 Sep;127(9):531-6. doi: 10.1007/s004320100265.
Alterations in the cell cycle regulatory cyclin/retinoblastoma protein (pRB) pathway play a important role in tumor progression in esophageal squamous cell carcinoma (ESCC). In the present study, we evaluated the prognostic significance of the combined analysis of cyclin D1 and pRB in ESCC retrospectively.
Immunoreactivities of cyclin D1 and pRB were evaluated in 148 surgically resected ESCC by use of monoclonal antibodies. Disease-free survival of patients was compared among the four subgroups according to the phenotypes of cyclin D1 and pRB expressions.
High immunoreactivities of pRB and cyclin D1 were detected in 64.2% and 40.5% of tumors, respectively. The loss of pRB expression and overexpression of cyclin D1 correlated with short survival. However, these factors were not detected as independently prognostic in multivariate analysis. In 107 surviving patients who underwent curative operation, co-expressed pRB and cyclin D1 (pRB+/cyclin D1 +: 29 patients) were correlated with unfavorable prognosis (disease-free 5-year survival rate: 42.7%) and high cancer recurrence rate (44.8%) compared with that of 40 patients with pRB +/cyclin D1- tumors (70.5% and 27.5%). The disease-free 5-year survival rate of patients with pRB+/cyclin D1- tumors was significantly better than that of other groups (P=0.001). However, the disease-free 5-year survival rate of 29 patients with pRB+/cyclin D1 + tumors was equivalent to that of 29 patients with pRB-/cyclin D1tumors (48.3%), and that of nine patients with pRB-/cyclin D1+ tumors (22.2%, P=0.237).
Our results suggest that overexpression of cyclin D1 may suppress pRB function, and that combined analysis of pRB and cyclin D1 may be a useful parameter of patient prognosis in ESCC.
细胞周期调节因子细胞周期蛋白/视网膜母细胞瘤蛋白（pRB）通路的改变在食管鳞状细胞癌（ESCC）的肿瘤进展中起重要作用。在本研究中，我们回顾性评估了ESCC中细胞周期蛋白D1和pRB联合分析的预后意义。
使用单克隆抗体对148例手术切除的ESCC中细胞周期蛋白D1和pRB的免疫反应性进行评估。根据细胞周期蛋白D1和pRB表达的表型，比较四个亚组患者的无病生存期。
分别在64.2%和40.5%的肿瘤中检测到pRB和细胞周期蛋白D1的高免疫反应性。pRB表达缺失和细胞周期蛋白D1过表达与生存期短相关。然而，在多变量分析中，这些因素未被检测为独立的预后因素。在107例接受根治性手术的存活患者中，与40例pRB +/细胞周期蛋白D1-肿瘤患者（70.5%和27.5%）相比，共表达pRB和细胞周期蛋白D1（pRB+/细胞周期蛋白D1 +：29例患者）与不良预后（无病5年生存率：42.7%）和高癌症复发率（44.8%）相关。pRB+/细胞周期蛋白D1-肿瘤患者的无病5年生存率显著优于其他组（P = 0.001）。然而，29例pRB+/细胞周期蛋白D1 +肿瘤患者的无病5年生存率与29例pRB-/细胞周期蛋白D1-肿瘤患者（48.3%）以及9例pRB-/细胞周期蛋白D1+肿瘤患者（22.2%，P = 0.237）相当。
我们的结果表明，细胞周期蛋白D1的过表达可能抑制pRB功能，并且pRB和细胞周期蛋白D1的联合分析可能是ESCC患者预后的一个有用参数。
