Cyclin D1 expression in non-small-cell lung cancers: its association with altered p53 expression, cell proliferation and clinical outcome
Cyclin D1 expression in non-small-cell lung cancers: its association with altered p53 expression, cell proliferation and clinical outcome
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DOI：
10.1038/sj.bjc.6690500
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发表时间：
1999-06-01
影响因子：
8.8
通讯作者：
Kawakami, Y
中科院分区：
文献类型：
--
作者：
Mishina, T;Dosaka-Akita, H;Kawakami, Y
细胞周期蛋白D1与p16(INK4)(P16)和视网膜母细胞瘤(Rb)蛋白一样，参与了细胞周期调控的GI-S转换。我们以前已经证明了非小细胞肺癌(NSCLC)中p16和RE蛋白状态的改变以及它们与改变的p53蛋白对增殖活性的潜在协同作用(Kinoshita等人(1996)癌症资源56)。5557-5562)。本研究采用免疫组织化学方法检测了111例非小细胞肺癌手术切除标本中细胞周期蛋白D1的表达，并用Southern杂交分析了29例非小细胞肺癌中细胞周期蛋白D1基因的表达情况。分析细胞周期蛋白D1的表达与P53、p16和RE蛋白状态的关系，并用Ki-67指数测定细胞增殖活性。还分析了1990至1995年间有可能行根治性切除的77例非小细胞肺癌患者的生存情况。我们发现：(1)在111例非小细胞肺癌中，有13例(11.7%)表达细胞周期蛋白D1；(2)细胞周期蛋白D1基因未见明显扩增和重排；(3)细胞周期蛋白D1表达与p53蛋白表达变化显著相关(P=0.04)，与p16和RE蛋白状态无关；(4)细胞周期蛋白D1阳性(+)肿瘤的增殖活性高于细胞周期蛋白D1阴性(-)肿瘤，但差异无统计学意义(P=0.08)；(5)Cyclin D1+肿瘤患者的生存时间明显长于Cyclin D1-肿瘤患者(Kaplan-Meier法5年生存率分别为89%和%，LOG检验P=0.045)，Cyclin D1表达是影响预后的因素(单因素分析P=0.08)。这些结果提示细胞周期蛋白D1参与了非小细胞肺癌的发生发展、增殖活性和临床转归。
Cyclin D1, like p16(INK4) (p16) and retinoblastoma (RB) proteins, participates in the cell cycle control at the GI-S transition. We have previously demonstrated altered p16 and RE protein status in non-small-cell lung cancers (NSCLCs) and their potential synergistic effect with altered p53 protein on proliferative activity (Kinoshita et al (1996) Cancer Res 56. 5557-5562). In the present study, cyclin D1 expression was studied by immunohistochemistry in the same cohort of 111 resected NSCLCs as in our previous study, and the amount of the cyclin D1 gene was analysed by Southern blot analysis in 29 NSCLCs. Cyclin D1 expression was analysed in relation to the status of p53, p16 and RE proteins, and proliferative activity determined by the Ki-67 index. It was also analysed in relation to survival of 77 patients with NSCLCs which were potentially curatively resected between 1990 and 1995. We found that: (1) cyclin D1 was expressed in 13 (11.7%) of 111 NSCLCs; (2) the cyclin D1 gene was neither significantly amplified nor rearranged; (3) cyclin D1 expression significantly correlated with altered p53 protein expression (P = 0.04), whereas it did not correlate with p16 and RE protein status, (4) proliferative activity tended to be higher in cyclin D1-positive (+) tumours than in cyclin D1-negative (-) tumours, although this difference was not statistically significant (P = 0.08); and (5) patients with cyclin D1+ tumours survived longer than patients with cyclin D1- tumours (5-year survival rates, 89% and 64% respectively, by the Kaplan-Meier method; P = 0.045 by the log-rank test), and cyclin D1 expression tended to be a favourable prognostic factor (P = 0.08 in univariate analysis). These findings suggest the involvement of cyclin D1 in the development and progression of NSCLCs, their proliferative activity and clinical outcome of NSCLC patients.