Institute of Medicine, Section of Oncology, University of Bergen, Bergen 5021, Norway.
Br J Cancer. 2012 Nov 6;107(10):1684-91. doi: 10.1038/bjc.2012.463. Epub 2012 Oct 25.
The aim of this study was to investigate the value of the cyclin D1 isoforms D1a and D1b as prognostic factors and their relevance as predictors of response to adjuvant chemotherapy with 5-fluorouracil and levamisole (5-FU/LEV) in colorectal cancer (CRC).
Protein expression of nuclear cyclin D1a and D1b was assessed by immunohistochemistry in 335 CRC patients treated with surgery alone or with adjuvant therapy using 5-FU/LEV. The prognostic and predictive value of these two molecular markers and clinicopathological factors were evaluated statistically in univariate and multivariate survival analyses.
Neither cyclin D1a nor D1b showed any prognostic value in CRC or colon cancer patients. However, high cyclin D1a predicted benefit from adjuvant therapy measured in 5-year relapse-free survival (RFS) and CRC-specific survival (CSS) compared to surgery alone in colon cancer (P=0.012 and P=0.038, respectively) and especially in colon cancer stage III patients (P=0.005 and P=0.019, respectively) in univariate analyses. An interaction between treatment group and cyclin D1a could be shown for RFS (P=0.004) and CSS (P=0.025) in multivariate analysis.
Our study identifies high cyclin D1a protein expression as a positive predictive factor for the benefit of adjuvant 5-FU/LEV treatment in colon cancer, particularly in stage III colon cancer.
本研究旨在探讨细胞周期蛋白 D1 异构体 D1a 和 D1b 作为预后因素的价值及其作为结直肠癌（CRC）患者接受氟尿嘧啶和左旋咪唑（5-FU/LEV）辅助化疗反应预测因子的相关性。
采用免疫组织化学法检测 335 例单独手术或接受 5-FU/LEV 辅助治疗的 CRC 患者中核细胞周期蛋白 D1a 和 D1b 的蛋白表达。采用单因素和多因素生存分析评估这两个分子标志物和临床病理因素的预后和预测价值。
在 CRC 或结肠癌患者中，细胞周期蛋白 D1a 和 D1b 均无预后价值。然而，与单独手术相比，高细胞周期蛋白 D1a 预测辅助治疗可改善 5 年无复发生存（RFS）和 CRC 特异性生存（CSS），在结肠癌（P=0.012 和 P=0.038），特别是结肠癌 III 期患者（P=0.005 和 P=0.019），单因素分析中差异有统计学意义。多因素分析显示，治疗组与细胞周期蛋白 D1a 之间存在交互作用，可影响 RFS（P=0.004）和 CSS（P=0.025）。
本研究确定高细胞周期蛋白 D1a 蛋白表达为氟尿嘧啶和左旋咪唑辅助治疗结肠癌，特别是结肠癌 III 期患者获益的阳性预测因子。
