Tonini G, Vincenzi B, Santini D, Scarpa S, Vasaturo T, Malacrino C, Coppola R, Magistrelli P, Borzomati D, Baldi A, Antinori A, Caricato M, Nuzzo G, Picciocchi A
Medical Oncology, University Campus Bio-Medico, Rome, Via Emilio Longoni 83, 00155 Rome, Italy.
Br J Cancer. 2005 Jun 20;92(12):2225-32. doi: 10.1038/sj.bjc.6602632.
Pancreatic cancer is one of the most aggressive gastrointestinal cancer with less than 10% long-term survivors. The apoptotic pathway deregulation is a postulated mechanism of carcinogenesis of this tumour. The present study investigated the prognostic role of apoptosis and apoptosis-involved proteins in a series of surgically resected pancreatic cancer patients. All patients affected by pancreatic adenocarcinoma and treated with surgical resection from 1988 to 2003 were considered for the study. Patients' clinical data and pathological tumour features were recorded. Survivin and Cox-2 expression were evaluated by immunohistochemical staining. Apoptotic cells were identified using the TUNEL method. Tumour specimen of 67 resected patients was included in the study. By univariate analysis, survival was influenced by Survivin overexpression. The nuclear Survivin overexpression was associated with better prognosis (P = 0.0009), while its cytoplasmic overexpression resulted a negative prognostic factor (P = 0.0127). Also, the apoptotic index was a statistically significant prognostic factor in a univariate model (P = 0.0142). By a multivariate Cox regression analysis, both the nuclear (P = 0.002) and cytoplasmic (P = 0.040) Survivin overexpression maintained the prognostic statistical value. This is the first study reporting a statistical significant prognostic relevance of nuclear and cytoplasmic Survivin overexpression in pancreatic cancer. In particular, patients with high nuclear Survivin staining showed a longer survival, whereas patients with high cytoplasmic Survivin staining had a shorter overall survival.
胰腺癌是侵袭性最强的胃肠道癌症之一,长期生存率不足10%。凋亡途径失调被认为是该肿瘤发生的一种机制。本研究调查了凋亡及凋亡相关蛋白在一系列手术切除的胰腺癌患者中的预后作用。本研究纳入了1988年至2003年期间所有接受手术切除治疗的胰腺腺癌患者。记录患者的临床资料和肿瘤病理特征。通过免疫组化染色评估生存素和环氧合酶-2(Cox-2)的表达。使用末端脱氧核苷酸转移酶介导的缺口末端标记法(TUNEL法)鉴定凋亡细胞。67例手术切除患者的肿瘤标本纳入本研究。单因素分析显示,生存素过表达影响生存。细胞核生存素过表达与较好的预后相关(P = 0.0009),而其细胞质过表达则是一个负性预后因素(P = 0.0127)。此外,在单因素模型中,凋亡指数也是一个具有统计学意义的预后因素(P = 0.0142)。多因素Cox回归分析显示,细胞核(P = 0.002)和细胞质(P = 0.040)生存素过表达均保持预后统计学价值。这是第一项报道细胞核和细胞质生存素过表达在胰腺癌中具有统计学显著预后相关性的研究。特别是,细胞核生存素染色高的患者生存期较长,而细胞质生存素染色高的患者总生存期较短。