Expression and gene amplification of primary (A, B1, D1, D3, and E) and secondary (C and H) cyclins in colon adenocarcinomas and correlation with patient outcome
Expression and gene amplification of primary (A, B1, D1, D3, and E) and secondary (C and H) cyclins in colon adenocarcinomas and correlation with patient outcome
复制标题
DOI：
10.1136/jcp.2004.020347
复制
发表时间：
2005-05-01
影响因子：
3.4
通讯作者：
Bukholm, IRK
中科院分区：
文献类型：
--
作者：
Bondi, J;Husdal, A;Bukholm, IRK
背景/目的：细胞周期调控失调是癌症的一个标志。初级细胞周期蛋白（A，B1，D1，D3和E）对细胞周期进程至关重要。次级细胞周期蛋白（C和H）对细胞周期进程具有假定的间接影响，并且先前未在结肠癌中进行评估。本研究探讨细胞周期蛋白的蛋白表达和基因扩增在结肠腺癌和患者outcome.Methods：免疫组化和真实的时间定量聚合酶链反应检测细胞周期蛋白的表达和基因扩增在219肿瘤和患者预后的相关性。结果：细胞周期蛋白H过表达在所有的肿瘤，细胞周期蛋白C在88%，细胞周期蛋白B1在58%，细胞周期蛋白A在83%，细胞周期蛋白D3在36%，细胞周期蛋白E在25%，细胞周期蛋白D1在11%的肿瘤。在6.2%的肿瘤中观察到细胞周期蛋白A的额外基因拷贝，细胞周期蛋白B1为9%，细胞周期蛋白C为26.9%，细胞周期蛋白D1为55%，细胞周期蛋白D3为20.5%，细胞周期蛋白E为19.1%，细胞周期蛋白H为5.1%。蛋白质过表达和基因扩增之间的显着相关性被视为只有细胞周期蛋白C。细胞周期蛋白A的高表达与生存率的提高独立相关。细胞周期蛋白C的扩增与不良预后独立相关。结论：细胞周期蛋白C基因的扩增与不良预后相关，细胞周期蛋白A的高蛋白表达与结肠腺癌的预后较好相关。
Background/Aims: Deregulation of cell cycle control is a hallmark of cancer. The primary cyclins ( A, B1, D1, D3, and E) are crucial for cell cycle progression. Secondary cyclins ( C and H) have putative indirect effects on cell cycle progression and have not previously been evaluated in colon cancer. This study examined cyclin protein expression and gene amplification in colon adenocarcinoma and the correlation with patient outcome.Methods: Immunohistochemistry and real time quantitative polymerase chain reaction were used to determine cyclin expression and gene amplification in 219 tumours. The results were compared with clinical variables and patient outcomes.Results: Cyclin H was overexpressed in all tumours, cyclin C in 88%, cyclin B1 in 58%, cyclin A in 83%, cyclin D3 in 36%, cyclin E in 25%, and cyclin D1 in 11% of the tumours. Extra gene copies of cyclin A were seen in 6.2% of the tumours, cyclin B1 in 9%, cyclin C in 26.9%, cyclin D1 in 55%, cyclin D3 in 20.5%, cyclin E in 19.1%, and cyclin H in 5.1%. A significant correlation between protein overexpression and gene amplification was seen for cyclin C only. High expression of cyclin A was independently associated with improved survival. Amplification of cyclin C was independently associated with an unfavourable prognosis.Conclusions: Amplification of the cyclin C gene was related to an unfavourable prognosis and high protein expression of cyclin A was associated with a better outcome in colon adenocarcinoma.