Chadha Krishdeep S, Khoury Thaer, Yu Jihnhee, Black Jennifer D, Gibbs John F, Kuvshinoff Boris W, Tan Dongfeng, Brattain Michael G, Javle Milind M
Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, New York 14263, USA.
Ann Surg Oncol. 2006 Jul;13(7):933-9. doi: 10.1245/ASO.2006.07.011. Epub 2006 May 22.
Long-term survival of surgically resectable pancreatic cancer patients is uncommon. The epidermal growth factor receptor (EGFR) and the phosphoinositol-3-kinase pathways are often activated in pancreatic cancer, and an understanding of their role in resected cases may help refine adjuvant therapy.
We investigated the expression of EGFR, Erk, Akt, and their phosphoforms (p-) in pancreatectomy specimens and correlated these with survival. Thirty-nine consecutive surgically resected pancreatic adenocarcinoma cases were included. Immunohistochemical staining of paraffin-embedded blocks was performed by using monoclonal antibodies against EGFR, Erk, p-Erk, Akt, and p-Akt. A standard immunoperoxidase technique was used to detect the avidin-biotin peroxidase complex. Immunostaining was visually scored with the histoscore method by two surgical pathologists.
Patient characteristics were as follows: 17 men and 22 women; median age, 66 years; and American Joint Committee on Cancer stage I, 5 patients; stage II, 4 patients; stage III, 27 patients; and stage IV, 3 patients. The tumor was World Health Organization grade 1 in 4, grade 2 in 17, and grade 3 in 18 cases. Adjuvant therapies were chemotherapy (n = 6), radiotherapy (n = 1), and chemoradiotherapy (n = 17). Immunohistochemistry revealed positive expression of EGFR in 30.8%, Erk in 92.3%, p-Erk in 45.9%, Akt in 71.8%, and p-Akt in 20.5% of cases. On univariate analyses, tumor grade (P = .0098), p-Akt (P = .0003), and p-Erk (P = .0052) expression correlated with survival. On multivariate analyses, age (P = .0002; hazard ratio [HR], 1.8), grade (P = .00318; HR, 3.0), Akt (P = .0433; HR, .4), p-Akt (P = .0002; HR, .2), and p-Erk (P = .0003; HR, 3.5) expression correlated significantly with survival.
p-Erk and p-Akt expression may have prognostic and therapeutic implications in pancreatic cancer.
可手术切除的胰腺癌患者长期生存并不常见。表皮生长因子受体（EGFR）和磷酸肌醇-3-激酶通路在胰腺癌中常被激活，了解它们在切除病例中的作用可能有助于优化辅助治疗。
我们研究了EGFR、Erk、Akt及其磷酸化形式（p-）在胰腺切除标本中的表达，并将这些与生存情况相关联。纳入了39例连续接受手术切除的胰腺腺癌病例。通过使用针对EGFR、Erk、p-Erk、Akt和p-Akt的单克隆抗体对石蜡包埋块进行免疫组织化学染色。采用标准免疫过氧化物酶技术检测抗生物素蛋白-生物素过氧化物酶复合物。由两名外科病理学家采用组织评分法对免疫染色进行视觉评分。
患者特征如下：男性17例，女性22例；中位年龄66岁；美国癌症联合委员会分期I期5例，II期4例，III期27例，IV期3例。肿瘤世界卫生组织分级1级4例，2级17例，3级18例。辅助治疗包括化疗（n = 6）、放疗（n = 1）和放化疗（n = 17）。免疫组织化学显示，30.8%的病例EGFR呈阳性表达，92.3%的病例Erk呈阳性表达，45.9%的病例p-Erk呈阳性表达，71.8%的病例Akt呈阳性表达，20.5%的病例p-Akt呈阳性表达。单因素分析显示，肿瘤分级（P = .0098）、p-Akt（P = .0003）和p-Erk（P = .0052）表达与生存相关。多因素分析显示，年龄（P = .0002；风险比[HR]，1.8）、分级（P = .00318；HR，3.0）、Akt（P = .0433；HR，.4）、p-Akt（P = .0002；HR，.2）和p-Erk（P = .0003；HR，3.5）表达与生存显著相关。
p-Erk和p-Akt表达可能对胰腺癌具有预后和治疗意义。
