Detailed tissue expression of bcl-2, bax, bak and bcl-x in the normal human pancreas and in chronic pancreatitis, ampullary and pancreatic ductal adenocarcinomas
Detailed tissue expression of bcl-2, bax, bak and bcl-x in the normal human pancreas and in chronic pancreatitis, ampullary and pancreatic ductal adenocarcinomas
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DOI：
10.1159/000055820
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发表时间：
2001-01-01
期刊：
影响因子：
3.6
通讯作者：
Neoptolemos, JP
中科院分区：
文献类型：
--
作者：
Evans, JD;Cornford, PA;Neoptolemos, JP
背景本研究的目的是评估凋亡调节蛋白bcl-2家族在正常和患病的人胰腺组织中的表达。法采用免疫组化方法检测正常胰腺组织（n = 7）、慢性胰腺炎（n = 7）、胰腺导管腺癌（n = 23）和壶腹癌（n = 7）石蜡包埋标本中bcl-2、bax、bcl-x、巴克和p53的表达。结果如下：在正常胰腺和慢性胰腺炎组织中，bcl-2、bax和bcl-x主要表达于导管上皮细胞，而p53未检测到。bcl-2在胰腺导管腺癌和壶腹癌中的表达与正常腺泡（P < 0.01）、小导管（P < 0.001）和大导管（P < 0.01）相比均为阴性。Bax表达在小导管中减少（P < 0.01），但与正常腺泡或大导管无差异。巴克和bcl-x在恶性上皮中的表达高于腺泡和大导管上皮，而在小导管上皮中的表达低于腺泡和大导管上皮（P < 0.01）。23例胰腺癌中11例（48%）和7例壶腹癌中4例（57%）p53过表达。bcl-x表达的相对水平而不是bax或巴克的相对水平预测了个体患者的不同生存期，因此bcl-x强表达与术后中位生存期171天相关，而bcl-x表达减弱的患者术后中位生存期为912天（p < 0.001）。结论：胰腺癌和壶腹癌与bcl-2表达缺失有关。Bax、巴克和Bcl-x的表达与正常的小导管相比降低，而与大导管相比巴克和Bcl-x的表达增加。bcl-x表达与切除术后的存活率相关，并可能代表潜在的预后标志物。版权所有（C）2001 S，Karger AG，巴塞尔和IAP。
Background. The aim of this study was to evaluate expression of the bcl-2 family of apoptosis regulating proteins in normal and diseased human pancreatic tissues. Method. Expression of bcl-2, bax, bcl-x, bak and p53 was determined in formalin-fixed paraffin wax-embedded archival specimens of normal pancreatic tissue (n = 7), chronic pancreatitis (n = 7), pancreatic ductal adenocarcinoma (n = 23) and ampullary cancer (n = 7) by immunohistochemistry using specific antibodies. Results: In normal pancreas and chronic pancreatitis tissues, bcl-2, bax and bcl-x were predominantly expressed in ductal epithelial cells while p53 was not detected. In pancreatic ductal adenocarcinorna and ampullary cancer, bcl-2 was not detected compared with expression seen in normal acini (p < 0.01), minor (p < 0.001) and major ducts (p < 0.01). bax expression was reduced with respect to minor ducts (p < 0.01) but no different from normal acini or major ducts. bak and bcl-x were more strongly expressed in malignant epithelia compared with acini and major ducts but reduced when compared with minor ducts (p < 0.01). Overexpression of p53 was identified in 11 (48%) of 23 pancreatic adenocarcinomas and 4 (57%) of 7 ampullary cancers. Differential survival of individual patients was predicted by the relative level of bcl-x expression but not bax or bak, such that strong expression of bcl-x was associated with a median postoperative survival of 171 days when compared with 912 days for diminished expression (p < 0.001) of bcl-x. Conclusion: Pancreatic and ampullary cancer are associated with absent bcl-2 expression. bax, bak and bcl-x expression was reduced compared with normal minor ducts whilst bak and bcl-x expression was increased when compared with major ducts. bcl-x expression correlates with survival following resection and may represent a potential prognosis marker. Copyright (C) 2001 S, Karger AG, Basel and IAP.