First Department of Pathology, Laiko Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece.
J Cancer Res Clin Oncol. 2010 Oct;136(10):1563-71. doi: 10.1007/s00432-010-0814-y. Epub 2010 Feb 20.
To elucidate the role of D-type cyclins in both superficial (Ta-T1) and muscle-invasive (T2-T4) urothelial carcinomas (UCs), investigating their potential prognostic usefulness.
Paraffin-embedded tissues from 157 patients with bladder UC were immunostained for cyclins D1, D2 and D3.
Cyclin D1 expression positively correlated with D2 and negatively with D3. Cyclin D1 expression decreased with increasing grade (P = 0.0001) and tumour T-category in the entire cohort and in muscle-invasive carcinomas (P = 0.0001 and P = 0.0033). Cyclin D2 correlated with grade (P = 0.0005) and T-category (P = 0.0078), a relationship which remained significant in muscle-invasive (P = 0.0135). Cyclin D3 immunoreactivity increased with histologic grade and T-category in the entire cohort (P = 0.0001 in both relationships), in superficial (P = 0.0034) and in muscle-invasive carcinomas (P = 0.0036, respectively). Survival analysis in superficial tumours showed that higher cyclin D1 (P = 0.0001) and higher cyclin D3 levels (P = 0.0032) were correlated with a lesser probability of survival. In muscle-invasive tumours, lower cyclin D1 (P = 0.0234), and D2 (P = 0.0424) and higher cyclin D3 (P = 0.0322) correlated with shortened survival. In multivariate analysis in superficial tumours only cyclin D3 expression remained significant. Cyclin D3 expression also retained its adverse significance in muscle-invasive tumours.
Cyclin D1 overexpression seems to be more important during early T-categories of bladder carcinogenesis, whereas cyclin D3 is implicated in the acquisition of a more aggressive phenotype. Cyclin D3 overexpression emerges as an independent adverse prognostic marker in both superficial and muscle-invasive tumours. Cyclin D1 is an independent indicator of shortened survival only in muscle-invasive tumours.
阐明 D 型细胞周期蛋白在表浅性（Ta-T1）和肌层浸润性（T2-T4）膀胱癌中的作用，探讨其潜在的预后价值。
对 157 例膀胱癌患者的石蜡包埋组织进行细胞周期蛋白 D1、D2 和 D3 的免疫组织化学染色。
细胞周期蛋白 D1 的表达与 D2 呈正相关，与 D3 呈负相关。在整个队列和肌层浸润性膀胱癌中，细胞周期蛋白 D1 的表达随着分级（P = 0.0001）和肿瘤 T 分期的增加而降低（P = 0.0001 和 P = 0.0033）。细胞周期蛋白 D2 与分级（P = 0.0005）和 T 分期（P = 0.0078）相关，这种关系在肌层浸润性肿瘤中仍然显著（P = 0.0135）。在整个队列中，细胞周期蛋白 D3 的免疫反应性随着组织学分级和 T 分期的增加而增加（在这两种关系中 P = 0.0001），在表浅性肿瘤（P = 0.0034）和肌层浸润性肿瘤（P = 0.0036）中也是如此。在表浅性肿瘤的生存分析中，较高的细胞周期蛋白 D1（P = 0.0001）和较高的细胞周期蛋白 D3 水平（P = 0.0032）与生存概率降低相关。在肌层浸润性肿瘤中，较低的细胞周期蛋白 D1（P = 0.0234）、D2（P = 0.0424）和较高的细胞周期蛋白 D3（P = 0.0322）与生存时间缩短相关。在表浅性肿瘤的多变量分析中，只有细胞周期蛋白 D3 的表达仍然具有显著性。在肌层浸润性肿瘤中，细胞周期蛋白 D3 的表达仍然具有不良预后意义。
细胞周期蛋白 D1 的过度表达似乎在膀胱癌早期 T 分期中更为重要，而细胞周期蛋白 D3 则与获得更具侵袭性的表型有关。细胞周期蛋白 D3 的过度表达在表浅性和肌层浸润性肿瘤中均成为独立的不良预后标志物。细胞周期蛋白 D1 仅在肌层浸润性肿瘤中是生存时间缩短的独立指标。
