Bold R J, Hess K R, Pearson A S, Grau A M, Sinicrope F A, Jennings M, McConkey D J, Bucana C D, Cleary K R, Hallin P A, Chiao P J, Abbruzzese J L, Evans D B
Pancreatic Tumor Study Group: Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
J Gastrointest Surg. 1999 May-Jun;3(3):263-77. doi: 10.1016/s1091-255x(99)80068-7.
The p53 tumor suppressor gene and the Bcl-2 proto-oncogene regulate cell cycle progression and apoptosis. We evaluated the expression of these molecular markers with standard pathologic prognostic variables in patients who received multimodality therapy for resectable adenocarcinoma of the pancreas to study the effect of p53 and Bcl-2 on survival duration. Immunohistochemical staining of archival material was performed to determine levels of expression of p53 and Bcl-2 proteins in 70 patients with adenocarcinoma of pancreatic origin. All patients underwent a potentially curative pancreaticoduodenectomy and standardized pathologic analysis of resected specimens. Potential pathologic and molecular prognostic variables were assessed for their effect on survival duration. Nuclear staining for p53 was observed in 33 (47%) of 70 specimens. Immunostaining for Bcl-2 was observed in 23 specimens (33%). A trend toward improved survival duration was seen in patients whose tumors stained positive for either p53 or Bcl-2. Negative staining for both markers predicted short survival (P = 0.01). By univariate and multivariate analyses, no single pathologic factor was associated with survival duration. Immunohistochemical staging using both p53 and Bcl-2 significantly predicted survival duration by univariate and multivariate analysis; patients whose tumors stained positively for p53 and/or overexpressed Bcl-2 had a significantly longer survival than those whose tumors stained negative for both proteins.
p53肿瘤抑制基因和Bcl-2原癌基因可调节细胞周期进程和细胞凋亡。我们在接受多模式治疗的可切除胰腺癌患者中,将这些分子标志物的表达与标准病理预后变量进行评估,以研究p53和Bcl-2对生存时间的影响。对存档材料进行免疫组织化学染色,以确定70例胰腺源性腺癌患者中p53和Bcl-2蛋白的表达水平。所有患者均接受了可能治愈性的胰十二指肠切除术,并对切除标本进行了标准化病理分析。评估潜在的病理和分子预后变量对生存时间的影响。在70个标本中的33个(47%)观察到p53的核染色。在23个标本(33%)中观察到Bcl-2的免疫染色。肿瘤p53或Bcl-2染色阳性的患者生存时间有延长趋势。两种标志物均为阴性染色预示着生存期短(P = 0.01)。通过单因素和多因素分析,没有单一病理因素与生存时间相关。使用p53和Bcl-2进行免疫组织化学分期,通过单因素和多因素分析均显著预测了生存时间;肿瘤p53染色阳性和/或Bcl-2过表达的患者比两种蛋白染色均为阴性的患者生存期明显更长。