Magistrelli Paolo, Coppola Roberto, Tonini Giuseppe, Vincenzi Bruno, Santini Daniele, Borzomati Domenico, Vecchio Fabio, Valeri Sergio, Castri Federica, Antinori Armando, Nuzzo Gennaro, Caraglia Michele, Picciocchi Aurelio
Department of Surgery, Catholic University School of Medicine, Rome, Italy.
J Cell Biochem. 2006 Jan 1;97(1):98-108. doi: 10.1002/jcb.20621.
In the present study, the prognostic impact of factors involved in the apoptosis pathway were tested on 67 consecutive patients treated with surgical resection. Included in the study were all patients resected for pancreatic adenocarcinoma from 1988 to 2003. Expression analysis for p53, Bax, and Bcl-2 were performed by immunohistochemical staining. Apoptotic cells were identified by the TUNEL method. These data were correlated with survival. Sixty-seven tumor specimens were included in the study. A strong positive correlation was recorded between p53 overexpression and Bax expression levels (P < 0.001). By univariate analysis, overall survival seemed to be improved with Bcl-2 and Bax expression (respectively, P = 0.0379 and 0.0311). The median survival time in patients with low apoptotic index was better versus those with a high index (P = 0.0127). Lymph node involvement was the only clinico-pathologic parameter that significantly correlated with overall survival (P = 0.0202). By a multivariate Cox regression analysis, the only immunohistochemical parameter that influenced overall survival was the apoptotic index (P = 0.040). Tumor's overexpression of both Bax and Bcl-2 resulted the strongest independent prognostic factor (P = 0.013). This is the first study to report a statistically significant association of apoptosis to overall survival for pancreatic cancer patients treated with surgical resection. The contemporary overexpression of Bax and Bcl-2 represents the strongest prognostic factor.
在本研究中,对67例接受手术切除治疗的连续患者测试了凋亡途径相关因素的预后影响。研究纳入了1988年至2003年期间所有因胰腺腺癌接受切除手术的患者。通过免疫组织化学染色对p53、Bax和Bcl-2进行表达分析。采用TUNEL法鉴定凋亡细胞。这些数据与生存率相关。本研究纳入了67个肿瘤标本。p53过表达与Bax表达水平之间存在强正相关(P < 0.001)。单因素分析显示,Bcl-2和Bax表达可改善总生存率(分别为P = 0.0379和0.0311)。凋亡指数低的患者中位生存时间优于凋亡指数高的患者(P = 0.0127)。淋巴结受累是唯一与总生存率显著相关的临床病理参数(P = 0.0202)。多因素Cox回归分析显示,唯一影响总生存率的免疫组化参数是凋亡指数(P = 0.040)。肿瘤同时过表达Bax和Bcl-2是最强的独立预后因素(P = 0.013)。这是第一项报道手术切除治疗的胰腺癌患者凋亡与总生存率存在统计学显著关联的研究。Bax和Bcl-2的同时过表达是最强的预后因素。