Keum J S, Kong G, Yang S C, Shin D H, Park S S, Lee J H, Lee J D
Department of Pathology, School of Medicine, Sungkyunkwan University, Seoul, Korea.
Br J Cancer. 1999 Sep;81(1):127-32. doi: 10.1038/sj.bjc.6690661.
Cyclin D1 is one of the G1 cyclins that control cell cycle progression by allowing G1 to S transition. Overexpression of cyclin D1 has been postulated to play an important role in the development of human cancers. We have investigated the correlation between cyclin D1 overexpression and known clinicopathological factors and also its prognostic implication on resected non-small-cell lung cancer (NSCLC) patients. Formalin-fixed and paraffin-embedded tumour tissues resected from 69 NSCLC patients between stages I and IIIa were immunohistochemically examined to detect altered cyclin D1 expression. Twenty-four cases (34.8%) revealed positive immunoreactivity for cyclin D1. Cyclin D1 overexpression is significantly higher in patients with lymph node metastasis (50.0% vs 14.4%, P = 0.002) and with advanced pathological stages (I, 10%; II, 53.8%; IIIa, 41.7%, P = 0.048; stage I vs II, IIIa, P = 0.006). Twenty-four patients with cyclin D1-positive immunoreactivity revealed a significantly shorter overall survival than the patients with negativity (24.0 +/- 3.9 months vs 50.1 +/- 6.4 months, P = 0.0299). Among 33 patients between stages I and II, nine patients with cyclin D1-positive immunoreactivity had a much shorter overall survival (29.7 +/- 6.1 months vs 74.6 +/- 8.6 months, P = 0.0066). These results suggest that cyclin D1 overexpression is involved in tumorigenesis of NSCLCs from early stage and could be a predictive molecular marker for poor prognosis in resectable NSCLC patients, which may help us to choose proper therapeutic modalities after resection of the tumor.
细胞周期蛋白D1是一种G1期细胞周期蛋白,通过促使G1期向S期转变来控制细胞周期进程。据推测,细胞周期蛋白D1的过表达在人类癌症发生过程中起重要作用。我们研究了细胞周期蛋白D1过表达与已知临床病理因素之间的相关性,以及其对接受手术切除的非小细胞肺癌(NSCLC)患者的预后影响。对69例I期至IIIa期NSCLC患者手术切除的福尔马林固定、石蜡包埋肿瘤组织进行免疫组织化学检测,以检测细胞周期蛋白D1表达的改变。24例(34.8%)显示细胞周期蛋白D1免疫反应阳性。细胞周期蛋白D1过表达在有淋巴结转移的患者中显著更高(50.0%对14.4%,P = 0.002),在病理分期较晚的患者中也显著更高(I期,10%;II期,53.8%;IIIa期,41.7%,P = 0.048;I期与II期、IIIa期相比,P = 0.006)。24例细胞周期蛋白D1免疫反应阳性的患者总生存期明显短于阴性患者(24.0±3.9个月对50.1±6.4个月,P = 0.0299)。在33例I期至II期患者中,9例细胞周期蛋白D1免疫反应阳性的患者总生存期更短(29.7±6.1个月对74.6±8.6个月,P = 0.0066)。这些结果表明,细胞周期蛋白D1过表达从早期就参与了NSCLC的肿瘤发生,并且可能是可切除NSCLC患者预后不良的预测分子标志物,这可能有助于我们在肿瘤切除后选择合适的治疗方式。