Dipartimento Medicina Sperimentale, Sapienza Università di Roma, Rome, Italy.
BJU Int. 2010 Sep;106(5):710-5. doi: 10.1111/j.1464-410X.2009.09130.x.
To evaluate the prognostic significance of survivin in tumour tissues and that of survivin-expressing circulating tumour cells (CTCs) in T1G3 bladder tumours, as the prognosis of T1G3 bladder cancer is highly variable and unpredictable from clinical and pathological prognostic factors.
The study included 54 patients with T1G3 non-muscle-invasive bladder cancer. Additional inclusion criteria were: tumour size <3 cm, absence of carcinoma in situ and multifocality. The planned follow-up was 24 months. Survivin was evaluated by reverse transcription-polymerase chain reaction in tumour tissues. CTCs were isolated from blood by CELLection Dynabeads (Invitrogen, Carlsbad, CA, USA) coated with the monoclonal antibody towards the human epithelial cell adhesion molecule. Cells were lysed and Dynabeads Oligo(dT) was used to capture poly A + mRNA. cDNA was synthesized and analysed for the expression of CD45, CK8 and survivin. The primary endpoint was disease-free survival (DFS); the favourable group at 24 months was defined as that with no clinical evidence of disease; the unfavourable group was that with evidence of recurrent disease or progressive disease. Tumour survivin expression and presence of CTC were correlated with DFS. Multivariate analysis was used to investigate whether the presence of CTC was an independent indicator of DFS.
Survivin was found in half of the tumours; patients with survivin-negative tumours had a longer DFS than those with survivin-positive tumours (chi-square, P = 0.029). CTCs were found in 24/54 patients (44%); 92% of CTC expressed survivin. The difference in DFS between CTC-ve and CTC+ve patients was statistically significant (chi-square, P < 0.001). The presence of CTC was an independent prognostic factor for DFS (P < 0.001).
The presence of CTC is an independent prognostic factor in patients with T1G3 bladder cancer.
评估肿瘤组织中生存素和 T1G3 膀胱癌中表达生存素的循环肿瘤细胞（CTC）的预后意义，因为 T1G3 膀胱癌的预后从临床和病理预后因素来看高度可变且不可预测。
本研究纳入了 54 例 T1G3 非肌肉浸润性膀胱癌患者。额外的纳入标准是：肿瘤大小<3cm，不存在原位癌和多灶性。计划随访 24 个月。通过逆转录-聚合酶链反应（RT-PCR）评估肿瘤组织中的生存素。通过 CELLection Dynabeads（ Invitrogen，Carlsbad，CA，USA）从血液中分离 CTC，该 Dynabeads 用针对人上皮细胞黏附分子的单克隆抗体包被。细胞被裂解，并用 Dynabeads Oligo（dT）捕获 Poly A+mRNA。合成 cDNA 并分析 CD45、CK8 和生存素的表达。主要终点是无病生存率（DFS）；24 个月时的有利组定义为无临床疾病证据；不利组为有复发或进展性疾病的证据。肿瘤生存素表达和 CTC 的存在与 DFS 相关。多变量分析用于研究 CTC 的存在是否是 DFS 的独立指标。
一半的肿瘤中发现了生存素；肿瘤中生存素阴性的患者比生存素阳性的患者 DFS 更长（卡方，P=0.029）。在 54 例患者中发现了 24 例 CTC（44%）；92%的 CTC 表达生存素。CTC-ve 和 CTC+ve 患者之间 DFS 的差异具有统计学意义（卡方，P<0.001）。CTC 的存在是 DFS 的独立预后因素（P<0.001）。
在 T1G3 膀胱癌患者中，CTC 的存在是独立的预后因素。
