Apoptosis and expression of Bcl-2 and Bax proteins in invasive ductal carcinoma of the pancreas
Apoptosis and expression of Bcl-2 and Bax proteins in invasive ductal carcinoma of the pancreas
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DOI：
10.1097/00006676-200104000-00002
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发表时间：
2001-04-01
期刊：
影响因子：
2.9
通讯作者：
Tamura, K
中科院分区：
文献类型：
--
作者：
Nio, Y;Iguchi, C;Tamura, K
Bcl-2基因家族在细胞凋亡的调控中起着重要的作用。本研究旨在探讨胰腺浸润性导管癌（IDC）中细胞凋亡及凋亡抑制蛋白Bcl-2（pBcl-2）和凋亡促进蛋白Bax（pBax）表达的临床病理意义。本研究包括1982年至1998年间切除的66例IDC。原位缺口末端标记法检测细胞凋亡，免疫组化染色检测pBcl-2和pBax。凋亡以凋亡指数（AI，凋亡细胞占总肿瘤细胞的百分比）定量，并且在66个IDC中的26个（39%）中观察到高AI（>10%）。Al与淋巴结受累程度显著相关。pBax阳性表达率为64%（42/66），pBax表达与性别、淋巴结转移程度呈负相关。pBcl-2在16例IDC中表达（24%），但与临床病理因素无相关性。凋亡指数与pBcl-2、pBax表达无相关性，但与pBcl-2、pBax表达显著相关; 16例pBcl-2（+）IDC中15例同时为pBax（+），仅1例pBcl-2（+）IDC为pBax（-）。单因素分析显示细胞凋亡程度对患者预后无明显影响。pBax或pBcl-2表达与较好的预后显著相关，特别是pBax（+）pBcl-2（+）组的生存率显著高于其他组。另一方面，辅助化疗（ACT）组的生存曲线也高于单纯手术（SA）组，具有临界统计学意义。对于pBax（+）IDC患者，ACT组的生存率明显优于SA组，但ACT组中Al和pBcl-2表达与生存率的改善无关。多变量分析显示AI、pBcl-2表达和pBax表达本身并不代表IDC所致死亡的显著变量，但pBax表达与ACT疗效显著相关。pBax的表达可能是pBcl-2表达所必需的。pBcl-2和pBax的表达不是IDC患者的显著预后因素，但pBax的表达可能有助于预测ACT对IDC患者的影响。
The Bcl-2 family of genes plays important roles in the regulation of apoptosis. The present study was designed to assess the clinicopathologic significance of apoptosis and the expression of the apoptosis-inhibitory Bcl-2 protein (pBcl-2) and the apoptosis-promoting Bax protein (pBax) in human invasive ductal carcinomas (IDCs) of the pancreas. The present study included 66 IDCs that were resected between 1982 and 1998. Apoptosis was assessed by the in situ nick end labeling method and pBcl-2 and pBax were stained immunohistochemically. Apoptosis was quantified as the apoptotic index (AI, the percentage of apoptotic cells of the total tumor cells), and a high AI (>10%) was observed in 26 of the 66 (39%) IDCs. The Al correlated significantly with the extent of nodal involvement. pBax immunoreactivity was detected in 42 of 66 IDCs (64%), and pBax expression was significantly correlated with female gender and showed a significant negative correlation with the extent of nodal involvement. pBcl-2 was expressed in 16 IDCs (24%) but did not show any correlation with the clinicopathologic factors. The AI did not correlate with the expression of pBcl-2 or pBax, but there was a significant correlation between the expression of pBcl-2 and that of pBax; 15 of the 16 pBcl-2(+)IDCs were also pBax(+), and only one pBcl-2(+)IDC was pBax(-). Univariate analysis demonstrated that the degree of apoptosis had no significant influence on the patients' prognosis. pBax or pBcl-2 expression was significantly associated with a better prognosis, and in particular, the pBax(+)pBcl-2(+) group had a significantly higher survival than the other groups. On the other hand, the survival curve of the adjuvant chemotherapy (ACT) group was also higher than that of the surgery alone (SA) group, with borderline statistical signfiicance. The ACT group showed a significantly better survival rate than the SA group for the pBax(+)IDC patients, but the Al and pBcl-2 expression were not correlated with an improved survival rate in the ACT group. Multivariate analysis showed that the AI, pBcl-2 expression, and pBax expression by themselves did not represent significant variables for death owing to IDC, but pBax expression was significantly associated with the efficacy of ACT. In conclusion, pBax expression may be essential for pBcl-2 expression. pBcl-2 and pBax expressions are not significant prognostic factors for patients with IDC, but pBax expression may be beneficial in predicting the effects of ACT on patients with IDC.